FR2983873A1 - Use of expression level of genes comprising e.g. prosaposin-like 1, keratin associated protein 19-5, calmodulin-like 5, lysozyme and matrix metalloproteinase-12, as a marker of abnormal desquamation of a scalp, preferably dandruff scalp - Google Patents

Abstract

Use of expression level of at least one gene (I) comprising prosaposin-like 1, calmodulin-like 5, phospholipase A2, group IIF, major histocompatibility complex, class II, DR alpha, chemokine (C-C motif) ligand 22, adrenomedullin, lysozyme, matrix metalloproteinase-12, keratin associated protein 19-5, keratin associated protein 7-1 or G-protein-coupled receptors-109B, as a marker of abnormal desquamation of a scalp, preferably dandruff scalp, is claimed. Independent claims are included for: (1) screening genes to prevent and/or treat abnormal desquamation of the scalp, preferably dandruff scalp, comprising providing cells, preferably epithelial cells capable of expressing (I), contacting the cells with a test compound, or a combination of tested compound, measuring the expression level of the gene, and comparing, for each of the tested genes, the measured expression level with a reference value of the tested gene; (2) evaluating the effect of a cosmetic or dermatological treatment with the gene able to prevent or treat abnormal desquamation of the scalp, preferably dandruff scalp, comprising determining the expression level of genes from epithelial cells and comparing the expression level of genes with the reference value; and (3) in vitro or ex vivo cosmetic and non-therapeutic method to characterize the effectiveness of the cosmetic treatment of the scalp, preferably treatment of the abnormal desquamation of the scalp, comprising performing, before the implementation of cosmetic treatment, in a first isolated skin sample, preferably isolated scalp collected from the individual, and first measuring the expression level of the genes, performing after implementation of cosmetic treatment in a second isolated skin sample, preferably isolated scalp collected from the individual and a second measuring the expression level of the genes, comparing the first and second measurements, preferably to deduce the information relating to the effect of implementation of cosmetic treatment. ACTIVITY : Dermatological. MECHANISM OF ACTION : Gene therapy.

Description

The present invention relates to the field of prevention and / or treatment of anomalous desquamation of the scalp, and preferably of a dandruff condition of the scalp. The skin is a tissue whose cells are contiguous and integral with each other. It forms an outer coating comprising sebaceous or sweat glands, and hair follicles. The skin, and especially the scalp, are epithelia with continual renewal. Renewal, or desquamation, is a coordinated and finely regulated process resulting in the elimination of surface cells, insensitively and nonvisibly. However, abnormal or irregular desquamation of the stratum corneum cells, for various reasons, can lead to the formation of large, thick, visible to the naked eye cells called "dander" or "dandruff" as part of the scalp, or in other situations, thinning of the stratum corneum. The desquamation disorders, resulting from abnormal or irregular desquamation, can lead to a fragility, even a defect of the barrier properties of the epidermis.

As an example of factors promoting the appearance of dander or dandruff, mention may be made of stress, the winter period, an excess of sebum, a lack of hydration, or the colonization of the skin or hair follicles paria yeast Malassezia sp .. These factors have, in particular, for common character to cause and / or promote an inflammatory skin condition. Such inflammation enhances the appearance or even increases the presence of dander or dandruff. In particular, yeasts of the Malassezia sp. Type, constituting a part of the commensal flora normal to the surface of the scalp in subjects without film, see their proportion increase substantially in case of dandruff, or in case of associated seborrheic dermatitis. The imbalance of scalp ecoflora is a factor favoring or even reinforcing the presence of dandruff.

The presence of dander or dandruff can be chronic, frequent, recurrent, and socially disabling conditions because of their obvious unsightly nature. Moreover, the dandruff condition of the scalp or the abnormal desquamation of the skin can result in an alteration of the barrier function of the epidermis, or generate sensations of itching or pruritus, leading to scraping behaviors amplifying the phenomenon the appearance of scales or dandruff and, in turn, irritation of the scalp or skin. The dandruff conditions of the scalp may be of the fatty type or of the dry type. The dry dandruff conditions of the scalp are more frequently manifested, and are amplified, during disorders of the hydration of the skin, and in particular during severe dryness of the epidermis of the scalp. Also, the scalp is rich in sebaceous glands, a dandruff condition can develop more easily in the presence of excessive sebum and be more easily itchy. Thus, excessive secretion of sebum, or hyperseborrhoea, promotes the appearance of a fatty dandruff condition of the scalp, or oily dandruff, generally associated with discomfort, sensations of discomfort, aesthetic disorders, or even cutaneous pathology. The dandruff states generally respond to different local or systemic treatments. However, the effectiveness of these treatments is only suspensive and involves rigorous monitoring by the user (frequency of use and sufficient application time). However, a daily and long-term use of these treatments can lead to a phenomenon of habituation reducing their effectiveness, and generally associated with a phenomenon of rebound occurring at the end of the treatment. This phenomenon is manifested by a hyperseborrhea, aggravating the dandruff condition and altering the barrier function of the scalp. Furthermore, the aggressiveness of certain antidandruff active against epidermal cells or ecoflora of the scalp can also affect the barrier functions of the latter and cause worsening of the dandruff condition. Finally, the effectiveness of anti-dandruff treatments is often slow to develop and requires a rigorous application in the long term. This latency often leads to a failure to monitor treatment. As a result, many failures occur in the implementation of these treatments.

Many epidermal factors, whose expression, biological activity or maturation are altered, diminished or increased, are known to be involved, directly or indirectly, in the process of renewal, or desquamation of the skin, and in particular scalp. These factors can be used as biomarkers of the skin, as screening targets, or even as cosmetic actives. However, there are still many unknowns as to the intimate mechanism and factors involved in desquamation of the skin, and in particular in the appearance of dandruff. There is therefore a need for new biomarkers to characterize desquamation of the skin, and more specifically a dandruff condition of the scalp. There is still a need for new targets for the screening of active agents or physical treatments for the care of the skin, in particular for preventing and / or treating a desquamation disorder of the skin, and more particularly a condition dandruff of the scalp. There is still a need to dispose of new assets or new treatments. i, 13, and / or to treat a disorder of skin desquamation, and more particularly a dandruff condition of the scalp. There is still a need to to have new cosmetic targets for the care of the skin, in particular for the prevention and / or treatment of a desquamation disorder of the skin, and more particularly a dandruff condition of the scalp. There is also a need for new cosmetic treatments to prevent, reduce and / or treat dandruff conditions of the scalp that are effective and have no side effects that may affect good compliance. The object of the present invention is to satisfy these needs. Unexpectedly, it is shown according to the invention a relationship between (i) the level of expression of a plurality of specific genes and (ii) anomalous desquamation of the scalp, and preferably a skin condition of a leather scalp. Said plurality of genes includes the following genes: PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, 12, KRTAP19-5, KRTAP7-1, and GPR109B. Specifically, there is shown an increased level of expression of the above specific genes in subjects to whom a dandruff cosmetic treatment has been applied. The results obtained by the inventors show that the level of expression of each of the above genes, in particular by epithelial cells of the scalp, is indicative of the presence or absence of abnormal or irregular desquamation of the leather. 25, and in particular is indicative of the dandruff condition of a scalp. The results also show that the level of expression of a gene selected from the above genes, by cells capable of expressing said gene, can be used to determine the capacity of an environment to favor, or on the contrary to reduce or prevent, the occurrence of a dandruff condition of the scalp. In particular, it is shown that the level of expression of a gene selected from the above genes by cells capable of expressing said gene can be used to determine the capacity of a substance, or a combination thereof. of substances, to reduce or prevent the occurrence of a dandruff condition of the scalp. According to the invention, it is therefore provided with tools for selecting substances or combinations of substances capable of inducing an increase in the expression of at least one of the above genes as cosmetic active agents capable of preventing or treating a disease. The condition of the invention also provides tools for determining the risk of the occurrence of a dandruff condition in a subject. Thus, the present invention is, in particular, relating to the use of the expression level of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, FILA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5. , TAP7-1, and GPR109B, as a marker of anomalous desquamation of the scalp, and preferably of the dandruff condition of a scalp.The invention also relates to the use of the expression level of at least a gene chosen from the genes PSAPL1, CALML 5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, II '12, TAP19-5, KRTAP7-1, and GPR109B, for the screening of assets for preventing and / or treating abnormal desquamation of the scalp, and preferably a dandruff condition of the scalp. For the purposes of the invention, the term "prevent" refers to the action of reducing the risk of occurrence of an event. The invention also relates to the use of the expression level of at least one gene selected from the genes PSAPLI, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, r12, TAP19-5, KRTAP7- I, and GPRIO9B, to determine the effect of a cosmetic treatment on anomalous desquamation of the scalp, and preferably on a dandruff condition of the scalp. It also relates to a method for the screening of active agents for preventing and / or treating anomalous desquamation of the scalp, and preferably a dandruff condition of the scalp, in which the effect of candidate compounds on the rate is determined. expressing at least one of the above genes. The invention also relates to a method for determining the condition of the scalp of a subject, wherein the level of expression of at least one of the above genes is determined. In certain aspects, the invention also relates to the cosmetic use of a compound, or a combination of compounds, capable of inducing an increase in the level of expression of at least one gene among the PSAPLI, CALML5, PLA2G2F, FILA-DRA, CCL22, ADM, LYZ, 1'12, KRTAP19-5, KRTAP7-1, and GPR109B genes, as an active ingredient for preventing or treating abnormal desquamation of the scalp, and preferably a dandruff condition of a scalp.

It also relates to a cosmetic method for the prevention or treatment of an abnormal desquamation of the scalp, and preferably a dandruff condition of a scalp, comprising a step of administering to a subject of an active capable of inducing an increase in the level of expression of at least one gene among the PSAPLI, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, I P12, KRTAP19-5, TAP7-1, and GPR109B genes. Said active agent includes a compound, a combination of compounds, as well as compositions comprising said compound or combination of compounds.

Markers of the dermal state of a scalp A biomarker of the invention advantageously makes it possible to characterize the desquamation, in particular abnormal desquamation, of the scalp, and preferably a dandruff condition of the scalp. According to one embodiment of the invention, an increase or a decrease in the activity, the expression or the maturation of a biomarker of the invention may be indicative of abnormal or irregular desquamation of the scalp, and preferably a dandruff condition of the scalp. According to a preferred embodiment, an increase in the activity, expression or maturation of a biomarker of the invention may be indicative of a dandruff condition of the scalp. A biomarker may be used to characterize the effectiveness of a cosmetic treatment of the scalp, and particularly with regard to abnormal or irregular desquamation of the scalp. In particular, the cosmetic treatment whose effectiveness is characterized can be a treatment of a dandruff condition of the scalp.

An increase or decrease in the expression of the biomarker may be indicative of an effective cosmetic treatment, and in particular to exert a beneficial effect on abnormal or irregular desquamation of the scalp, and in particular with regard to a certain condition. dandruff of the scalp. A decrease or increase in biomarker expression may be determined by comparison to a measurement or reference value obtained by any method known to those skilled in the art. A "reference measurement" or "reference value" with respect to a given parameter, is a qualitative or quantitative measurement of this parameter carried out under "control" or "normal" conditions, for example determined in a reference sample , or determined for example in sample in the absence of a treatment alleged to have an effect on the parameter. Preferably, a reference measurement is statistical measurement, that is to say having been repeated on different samples so as to obtain an average.

The reference measurement can be performed in parallel or sequentially with the test measurement. It can also be a "historical" measure, that is to say carried out prior to the test measurement, and stored, for example in a database, for later use.

A comparison of the test measurement with a reference measurement, and an observation of a deviation or a lack of deviation between the two measurements, makes it possible to derive information as to the measured parameter, for example the decrease or the increase. the expression, the processing or the activity of an amino acid sequence or a nucleic acid sequence according to the invention.

When a biomarker of the invention used is the level of expression of a gene of interest, abnormal or irregular desquamation of the scalp may result in a deviation of the value of the expression level of said gene. advantage of a factor of at least 2 times, preferably at least 3 times, and more preferably at least 10 times the normal reference value determined for an unaffected scalp of a dandruff condition .

Genes with Expression Level Used as a Marker Each gene whose expression rate has been identified as a relevant marker for scalp condition is briefly documented below. Said genes are also called "genes of interest" in the present description.

In the uses, methods and kits defined in the present description, the markers described below may be used with one or more other markers, preferably one or more markers known in the state of the art. PSAPL1 PSAPL1, which is also designated "prosaposin-like 1", is a gene located on chromosome 4, mapped at the 4p16.1 locus, and the sequence of which is described in the databases, in particular under the numbers "Gene ID 768239". (NCBI base) PSAPL1 is transcribed, in particular, into a mRNA of 4700 base pairs, the sequence of which is described in particular in NM 001085382 (NCBI base), in particular PSAPL1 encodes a protein of 543 amino acids, the sequence of which is described in particular. No. AAH68579 (NCBI base) Nucleic acids selectively hybridizing with the mRNA generated by transcription of the PSAPLI gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset n. CALML5 CALML5, which is also designated "calmodulin-like 5", is a gene located on chromosome 10, mapped at the 10p15.1 locus, and the sequence of which is described in particular in the US Pat. Gene ID 51806 (Genbank database). CALML5 is transcribed, in particular, into a mRNA of 893 base pairs, the sequence of which is described in particular under NMR NM_017422 (NCBI base). CALML5 codes in particular a protein of 146 amino acids whose sequence is described under No. NP 059118 (Base NCBI).

Selectively hybridizing nucleic acids with the transcriptional gene generated by the CALML5 gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7931859".

PLA2G2F PLA2G2F, which is also designated "phospholipase A2, TIF group", is a gene located on chromosome 1, mapped at the 1p35 locus, and whose sequence is described in particular under No. Gene ID 64600 and No. AC 000133 and the n ° NC 000001 (NCBI base). PLA2G2F is transcribed in particular into mRNA of 2737 base pairs, the sequence of which is described in particular under No. NM 022819 (NCBI base). In particular, PLA2G2F encodes a protein of 211 amino acids, the sequence of which is described under NP-073730 (NVBD base) .Nucleic acids selectively hybridizing with the mRNA generated by transcription of the PLA2G2F gene include the nucleic probes included on the Human Gene 1.0 chip. ST marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7898616".

HLA-DRA HLA-DRA, which is also designated "major histocompatibility complex, class II, DR alpha, is a gene located on chromosome 6, mapped at the 6p21.3 locus, and whose sequence is described in particular under the No. Gene ID 3122 and (NCBI base) HLA-DRA is transcribed, in particular, into a 2737 base pair mRNA, the sequence of which is described in particular under NMR 019111 (NCBI base) .HLA-DRA code in particular for a protein of 211 amino acids, the sequence of which is described as NP-073730 (NCBI-base) .Nucleic acids selectively hybridizing with the transcription-generated mRNA of the HLA-DRA gene include the nucleic probes included on the commercially available Human Gene 1.0 ST chip. by the company A etrix, said probes being referenced "Probeset No. 8118548" CCL22 CCL22, which is also designated "chemokine (CC motif) ligand 22", is a gene located on chromosome 16, mapped at locus 16q13, and the sequence is described no especially under the No. NC 000016. CCL22 is transcribed in particular into a mRNA of 2933 base pairs described under No. NM_002990 (NCBI base). CCL22 encodes a protein of 293 amino acids, the sequence of which is described under No. NP_2981 (NCBI base). Nucleic acids selectively hybridizing with the mRNA generated by transcription of the CCL22 gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7996022". ADM ADM, which is also designated "adrenomedullin", is a gene located on chromosome 11, mapped at 11p15, and whose sequence is described in particular under No. NC 000011 (NCBI base). ADM is transcribed in particular into a m of 1449 base pairs described under NM 001124 (NCBI base). ADM codes in particular a protein of 185 amino acids, the sequence of which is described under NP_001115. Nucleic acids selectively hybridizing with the ADM gene transcription-generated mRNA include the nucleic probes included on the Human Gene 1.0 ST chip marketed by Affymetrix, said probes being referenced "Probeset No. 7938390".

LYZ LYZ, which is also called "lysozyme", is a gene located on chromosome 12; mapped at the locus 12q15, and whose sequence is described in particular under the No. NG_008195 (NCBI base). LYZ is transcribed in particular into a mRNA of 1516 base pairs described under NM 000239 (NCBI base). LYZ codes in particular a protein of 148 amino acids, the sequence of which is described under NP_000230. Nucleic acids selectively hybridizing with the mRNA generated by transcription of the LYZ gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7957023". MMP12 MMP12, which is also designated matrix metalloproteinase 12 (macrophage elastase), is a gene located on chromosome 11, mapped at locus 11q22, and whose sequence is described under NC_000011 (NCBI base). in a m of 1877 base pairs under No. NM_002426 (NCBI base) MMP12 codes in particular a protein of 470 amino acids described under NP-002417 (NCBI base) .Nucleic acids selectively hybridizing with the mRNA generated by transcription of the MMP 12 gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7951297" KRTAP19-5 KRTAP19-5, which is also designated "keratin" associated protein 19-5 ", is a gene located on chromosome 21, mapped at locus 21q22, and whose sequence is described under No. NC 000021 (base NCBI) .KRTAPI9-5 is transcribed in particular into a mRNA of 219 pair es of bases described under No. NM 181611 (NCBI base). KRTAP19-5 codes in particular a protein described under the NF # 853642 (NCBI base). Nucleic acids selectively hybridizing with mRNA generated by transcription of the KRTAP19-5 gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by Affymetrix, said probes being referenced "Probeset No. 8069838".

KRTAP7-1 KRTAP7-1, which is also referred to as "keratin associated protein 7-1", is a gene located on chromosome 21, mapped at locus 21q22, and whose sequence is described as NC 000021 (NCBI basis). and Gene ID 337878. KRTAP7-1 is transcribed in particular to a 708 base pair mRNA described under No. NM_181606 (NCB1 base). KRTAP7-1 codes in particular a protein of 87 amino acids, the sequence of which is described under No. NP 853637 (NCBI base). Nucleic acids selectively hybridizing with the mRNA generated by transcription of the KRTAP7-1 gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by A etrix, said probes being referenced "Probeset No. 8069868". GPRIO9B GPR109B, which is also designated HCAR3 or "Hydroxycarboxylic Acid receptor 3", is a gene located on chromosome 12, mapped at locus 12q24, and whose sequence is described under No. NC 000021 (NCBI base) and Gene ID 337878. GPR109B is transcribed in particular into a mRNA of 708 base pairs described under No. NM_006018 (NCBI base). GPRIO9B codes in particular a protein of 387 amino acids, whose sequence is described under No. P_49019 (UNIPROT base).

Nucleic acids selectively hybridizing with the mRNA generated by transcription of the GPR109B gene include the nucleic probes included on the Human Gene 1.0 ST chip marketed by the Affymetrix Company, said probes being referenced "Probeset No. 7967322".

Sample Expression levels are determined according to the invention from a "sample". Within the meaning of the invention, a "sample" includes (i) a biological sample comprising epithelial cells; (ii) a sample comprising RNA extracted from a set of epithelial cells and (iii) a sample comprising proteins produced by epithelial cells. Preferably, the epithelial cells are epithelial cells of the scalp. The epithelial cells of the scalp include primary cultured epithelial cells and epithelial cell lines.

In some embodiments, said set of cells is obtained by sampling from the scalp of a subject. In other embodiments, said set of cells is obtained after an in vitro cell culture step, and optionally incubating the cells with an active agent to be tested.

The epithelial cells of the scalp can be obtained (i) by taking a small number of hair with their bulb or (ii) by applying an adhesive tape on the surface of the scalp, a sampling technique that is also called "stripping". After their removal, the epithelial cells of the scalp can be directly subjected to the RNA extraction step, if appropriate after a period of storage at a low temperature, for example at a temperature below -10 ° C. This includes a temperature below -40 ° C, and a temperature below -80 ° C. In other embodiments, the epithelial cells of the scalp can be cultured in vitro, under defined culture conditions, for example in the presence of an active agent to be tested, before measuring the level of expression of the skin. at least one gene selected from the genes of interest defined in the present description. Epithelial cell lines include those that are commercially available, for example from the American Type Culture Collection (ATCC, USA).

The epithelial cells also include the cells constituting a dermis reconstituted and maintained in culture in vitro. Thus, a sample suitable for the invention may be an isolated skin sample taken from an individual or from a reconstructed skin model, in vitro. In general, the uses and methods of the invention have the advantage of being methods that do not involve an invasive operation or step for the human body. Expression level In the sense of the invertion, "expression" of a gene is understood to mean (i) the synthesis of an mRNA, by transcription of said gene, (ii) the synthesis of a protein encoded by said gene. For the purposes of the invention, the term "transcript" means a ribonucleic acid (RNA) resulting from the transcription of a gene. A gene can yield multiple transcripts or mRNAs by alternative splicing, each encoding a protein isoform, obtained after translation of the mRNA. RNA is provided by extraction from a set of cells, according to methods well known to those skilled in the art.

According to one aspect of the invention, the determination of the transcriptional levels of the mRNAs can be done on the whole m 'or on a characteristic portion of the mRNA. A characteristic portion is a portion including all or part of the exon (s) subject to the alternative splicing. Advantageously, the determination of the transcription levels can be carried out on a characteristic portion of the mRNAs by means of a method comprising a specific amplification step of this portion. The methods for detecting and measuring the amount of RNA or DNA are known to those skilled in the art. These methods encompass methods comprising (i) a step of extracting RNA from the cells contained in the sample to be analyzed, (ii) a step of hybridizing the RNA extracted in the previous step with a collection nucleic probes and (iii) a step of detecting and / or quantifying the complexes formed between said and said nucleic probes. This type of method is illustrated in the examples, in which is used, for the hybridization step, a support on which is immobilized a collection of nucleic probes 20 able to hybridize with at least one gene selected from the genes PSAPL1 , CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, I '12, KRTAP19-5, TAP7-1, and GPR109B. Preferentially, the nucleic probes are immobilized on the support in the form of an ordered matrix in which the position of each specific nucleic probe is known. In some embodiments, said carrier, which may also be referred to as a "PN chip" or "DNA microarray", comprises, for each target RNA, a plurality of nucleic probes of distinct sequences, which are suitable for hybridizing to a plurality of characteristic portions of said target RNA, or which are capable of hybridizing with a plurality of isoforms of said target RNA, which includes a plurality of isoforms resulting from a plurality of alternative splicing events . The examples illustrate measurements of the expression level of the PSAPL1, CALML5, PLA2G2F, FILA-D -, CCL22, ADM, LYZ, MMP12, KRTAPI9-5, KRTAP7-1, and GPR109B genes. by hybridization of cellular RNA, previously obtained by extraction, on a DNA chip of the "Genechip4I human Gene 1.0 ST" type sold by Affymetrix (Santa Clara, CA, USA). The hybridized Nc is quantified by measuring and integrating a fluorescence signal, for example using the Aixix Expression ConsoleTM computer program provided by A 'etrix. The methods for detecting and measuring the amount of RNA or DNA also include RT-PCT (for reverse transcriptase PCR) and qRT-PCR (for "quantitative reverse transcriptase PCR") methods. Real-Time PCR. For the implementation of these methods, a person skilled in the art can refer in particular to the work of Wang et al. (1989, Proc Natl Acad Sci USA, Vol 86: 917-921), de Wong et al. (2005, Bio Techniques, Vol 39 (1): 75-85), de Nolan et al. (2006, Nat Protoc, Vol 1 (3): 1559-1582) and Klinck et al. (2008, Cancer Research, Vol 68: 657-663), or a general review of these techniques published by Bustin (2000, Journal of Molecular Endocrinology, Vol 25: 169-193). The above methods include (i) a step of extracting the cellular mRNAs, (iii) a step of reverse transcription of the mRNA into DNA using a reverse transcriptase enzyme, and (iii) a step of amplification of the DNA obtained in the previous step, using appropriate nucleotide primers, before quantification of the amplified DNA. In general, are simultaneously amplified from the same sample (a) the DNA obtained by reverse transcription of the mRNA of interest and (b) a DNA or a plurality of - Ns obtained by reverse transcription of mRNA expressed from constitutively and consistently by the housekeeping genes, such as the RNAs encoded by the MRPL19, PUM1 and GADPH genes. The amplified DNA can be quantified after separation. by electrophoresis and, by measurement of the DNA bands, and the results for the mRNA (s) of interest expressed in relative values as compared with the mRNAs encoded by the housekeeping genes. In some embodiments, the step of separating the amplified DNAs is carried out by agarose gel electrophoresis, then staining the ethidium bromide DNA bands, before quantification of the IINs contained in the migration bands by densitometry. . In other embodiments, a micro-channel device is used in which a separation of the DNAs, amplified by capillary electrophoresis, is performed, then a quantification of the different DNAs separated by measurement of the signal emitted by these DNAs after illumination by a laser beam. Such a device may be the LabChipfâ apparatus, for example of the "GX" series, marketed by the Caliper LifeSciences Company (Hopkinton, MA, USA). In certain embodiments, the determination of transcriptional levels of the mRNAs of the genes under consideration may comprise a step of amplifying a characteristic portion of said mRNAs using a pair of distinct primers, respectively for the cDNAs obtained. from each of the distinct genes considered.

Different sense and antisense primers can be implemented in an RT-PCR reaction that is suitable for the invention, provided that they frame the characteristic part of the mRNA or cDNA. The choice of sense and antisense primers is guided in particular by the identity of the sequences to be amplified, for each of the genes of interest.

Sense and antisense primers suitable for the invention may be obtained by any method known to those skilled in the art, especially as described by Sambrook et al. (Molecular Cloning: A Laboratory Manual, 31 "ed., 2001, Cold Spring Harbor, NY) According to other embodiments of a method of the invention, the expression levels of the genes of interest consist of at a rate of production of a protein encoded by said gene of interest In these embodiments, said expression levels are determined by methods comprising a step of quantifying said protein by the cells contained in the sample at analyze.

Typically, a protein encoded by a gene of interest can be detected and quantified using ligand compounds specifically recognizing said protein. The ligand compounds of said protein of interest may be chosen from antibodies, nucleic aptamers and protein aptamers, the methods for obtaining them being well known to those skilled in the art.

In particular, nucleic aptamers specifically binding to said protein of interest can be obtained according to the SELEX technique described, for example, in US Pat. Nos. 5,475,096 and 5,270,163. Antibodies directed specifically against said protein of interest can also be prepared according to a wide variety of techniques known to those skilled in the art. Such antibodies include polyclonal antibodies and monoclonal antibodies, including antibodies obtained by genetic recombination. The antibodies can be obtained according to the teachings of Kohler and Milstein (1975, Nature, Vol 256: 495-497). They can be obtained by genetic cloning techniques from a single lymphocyte cell of an appropriately immunized animal, as described by Babcook et al. (1996, Proc Natl Acad Sci USA, Vol 93 (15): 7843-78841) or in PCT Application Nos. WO 92/02551, WO 2004/051268 and WO 2004/106377. They may be recombinant antibodies, in particular humanized antibodies, and may be obtained by the techniques described in US Pat. No. 5,585,089 or PCT Application No. WO 91/09967, or else in patent documents EP0546073. , US 5,545,806, US 5,569,825, US 5,625,126, US 5,633,425, US 5,661,016, US5,770,429, EP 0438474 and EP0463151. Said protein of interest can be detected and quantified according to techniques well known to those skilled in the art, such as, for example, according to an immunoblotting technique (also known as "Western Blotting"). Typically, the cellular proteins are subjected after extraction to an electrophoresis gel migration step, then the protein bands are incubated with the relevant antibodies, for example with a combination of antibodies respectively recognizing the proteins of interest to be detected. Said protein of interest is quantified, for example by measuring a detectable signal emitted by the antibodies used, for example by measuring a fluorescence signal, for example a fluorescence signal emitted by the relevant antibodies if said relevant antibodies are labeled, or a fluorescence signal emitted by second antibodies "anti-antibody" if second antibodies are used, the first or second antibodies being labeled with a chromophore or a fluorophore, or by measurement of aborbance if said first or second antibodies are coupled to an enzyme capable of catalyzing the formation of a light absorbing product at a given wavelength. Determination of the value of the level of expression According to one aspect of the invention, the determinations of the transcription rate of the mRNAs resulting from the transcription of the gene (s) of interest, selected from among the genes and the genes PSAPL1, CALML5, PLA2G2F, FILA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B can be implemented as a ratio. According to the same aspect of the invention, the production rates of the proteins encoded by the gene (s) of interest, chosen from among the genes, the PSAPL1, CALML5, PLA2G2F, HLA-DRA and CCL22 genes. , ADM, LYZ, I '12, KRTAP19-5, 7-RTAP7-1, and GPR109B., Can be implemented as a ratio. Advantageously, this ratio can be determined by establishing a ratio, for each gene considered, between a level of expression, for example a transcription level of the mRNA, measured for a first cellular state and a level of expression, for example a transcription level of the mRNA, measured for a second cellular state. Typically, the value of the expression level of a gene of interest or a first cellular state is used as the reference value, with which the value of the expression rate of said gene of interest for a second state is compared. to determine whether the level of expression of said gene has increased or decreased for the second cell state.

By "cellular state" is meant according to the invention a physiological or metabolic state of a cell or a set of cells, in a specific environment. For example, cellular state encompasses the physiological or metabolic state of a set of cells contained in a biological sample taken at a given moment from the scalp of a subject. In some embodiments, a first cellular state includes the physiological or metabolic state of a set of cells contained in a biological sample taken at a given time from the scalp of a subject having a dandruff state, and having received no dandruff treatment. In these embodiments, a second cellular state, to be compared with the first cellular state, encompasses the physiological or metabolic state of a set of cells contained in a biological sample taken at a given instant from the scalp of a patient. subject suffering from a dandruff condition, and having received no dandruff treatment. According to one alternative, a second cellular state, to be compared with the first cellular state, encompasses the physiological or metabolic state of a set of cells contained in a biological sample taken at a given moment from the scalp of a subject who is not affected by a dandruff condition. Also, a cellular state encompasses the physiological or metabolic state of a set of cells cultured in vitro, preferably scalp epithelial cells cultured in vitro, under defined culture conditions. According to this aspect, a first cellular state may be the physiological or metabolic state of a set of cells cultured in vitro, in the absence of presumed compound (s) capable (s) to prevent or treat a dandruff in a subject. A second cellular state, to be compared with the first cellular state, may then be the physiological or metabolic state of said set of cells cultured in vitro, in the presence of suspected compound (s) capable of preventing or treating a dandruff condition in a subject. For example, such levels of expression can be determined in cells placed under physiological conditions or conditions mimicking physiological conditions, and in the absence of external factors likely to affect these conditions. An external factor considered in the invention may be active agent presumed effective for preventing and / or treating a film condition. According to one aspect of the invention, in the practice of the invention for evaluating the efficacy of an active agent capable of preventing and / or treating a film state, a reference transcription level can be obtained by determining the expression level of the genes of interest, for example the transcription rate of the mRNAs resulting from the transcription of the genes of interest, in the absence of the active whose efficacy is to be evaluated. In particular, in the practice of the invention for screening an asset presumed to prevent and / or treat a dandruff condition of the scalp, a reference ratio can be determined by reproducing the screening protocol in the absence of the active to be screened. In particular, during the implementation of the invention for evaluating the effectiveness of an active agent intended to prevent and / or treat a dandruff condition of the scalp in an individual in need, a reference expression level may be used. to be determined in an isolated biological sample obtained from said individual, preferably a sample obtained by removing epithelial cells from the scalp, before the administration of the active ingredient. Alternatively, a baseline expression level can be determined in a set of untreated individuals whose efficacy is to be assessed. In the practice of the invention for evaluating the efficacy of an active agent for preventing and / or treating a dandruff condition of the scalp in an individual in need thereof, the reference expression level may, where appropriate, appropriate, be correlated to other parameters of the subject, such as age, weight or other physio-pathological parameters. According to one aspect of the invention, a deviation, and more specifically an increase, between a level of expression of at least one of the genes of interest determined in the presence of a presumed active agent with respect to a state scalp and a reference expression level of 2C 'is indicative of an active agent effect with respect to said dandruff condition of the scalp. According to another aspect of the invention, a deviation, and more specifically an increase, between a level of expression of at least one of the genes of specific interest in the presence of a presumed active agent with respect to a dandruff condition of the scalp and a baseline expression level is indicative of a sensitivity of the individual to anti-dandruff treatment. In some embodiments, depending on the degree of deflection of the expression level observed, a treated individual may be described as resistant, weakly resistant, weakly sensitive, or sensitive to anti-dandruff treatment. Methods and Uses It is recalled that the present invention relates to the use of the expression level of at least one gene, also designated "gene of interest", chosen from the genes PSAPL1, CALML5, PLA2G2F, FILA-DRA , CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B., As a marker for the dandruff condition of a scalp. The invention also relates to the use of the expression level of at least one gene chosen from the genes of interest above, for the screening of active agents intended to prevent and / or treat a dandruff condition of the scalp. The invention also relates to the use of the expression level of at least one gene chosen from the genes of interest above, to determine the effect of a cosmetic treatment on the dandruff condition of the scalp. According to the invention, "at least one gene" encompasses 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 genes out of the 13 genes of interest above, or else all 13 genes of interest above. In some embodiments, it may be advantageous to determine the level of expression of more than one gene of interest, in order to possibly increase the reliability of the use or the method in question.

Without wishing to be bound by any theory, the inventors believe less a characteristic of the use or of the method under consideration, among the sensitivity, the specificity, and the reproducibility, can be increased when said use or said method comprises determining the rate of expression of more than one of the genes of interest above, for example from 4, 5 or 6 genes among the genes of interest above.

In certain embodiments of said use or method, the level of expression that is determined is a level of transcription of said gene (s) of interest above. In other embodiments of said use or method, the level of expression that is determined is a rate of synthesis or production of a protein encoded by said gene (s) of interest above . The present invention also relates to a method for the screening of active agents for preventing and / or treating a dandruff condition of the scalp, comprising the following steps: a) providing cells capable of expressing at least one gene chosen from the PSAPL1 genes , CALML5, PLA2G2F, CCL22, ADM, LYZ, MMP12, KRTAPI9-5, KRTAP7-1, and GPR109B., B) contacting said cells with a test compound, or a combination of test compounds, e) measuring the expression rate of at least one gene chosen from the genes specified for step a); d) comparing, for each of the genes tested, the level of expression measured in step c) with a reference value of said gene; tested gene. The details of practical implementation of such a method have been described previously in the present description, as well as in the examples.

For carrying out the above screening method, the cells capable of expressing at least one gene of interest, among the above genes, which are provided in step a), are chosen from (i) epithelial cells obtained by sampling from the scalp, and (ii) an epithelial cell line. Most preferably, said gene (s) of interest has (have) not been artificially produced, for example by genetic recombination, in the genome of said cells. Thus, said gene (s) of interest whose expression rate is determined is (are) that (those) which are (are) present naturally in the genome of said cells. In some embodiments, the reference value of the level of expression of the tested gene (s) is the value of the level of expression of said gene (s) by epithelial cells of the scalp. a subject not affected by a pellicular state. In some embodiments, the reference value of the level of expression of the tested gene (s) is the value of the level of expression of said gene (s) by epithelial cells of the scalp. of a subject previously affected by a pellicular state, which has been solved by a suitable cosmetic treatment.

In some embodiments, the reference value of the level of expression of the tested gene (s) is the value of the level of expression of said gene (s) by epithelial cells of the scalp. a subject likely to be affected by a dandruff condition, but in which a film condition has not yet occurred. In some embodiments, the reference value of the level of expression of the tested gene (s) is the value of the level of expression of said gene (s) by epithelial cells of the scalp. a subject affected by a dandruff condition. In some embodiments, the above screening method comprises the following additional step: e) selecting said compound, or said combination of compounds, when the expression level measured in step c) is respectively greater or less than a reference value for cells incubated in the absence of test compound. In certain embodiments of step e), in which the reference value is obtained by determining the level of expression of said gene (s) of interest (i) by a set of epithelial cells of the scalp of a subject not affected by a dandruff or subject state in which a pellicular state has been resolved or (ii) by epithelial cells cultured in vitro in the absence of the compound or combination of compounds to be tested, said compound or said combination of compounds is selected when the value of the expression level measured in step c) of the above screening method is greater than said reference value. In certain embodiments of step e), in which the reference value is obtained by determining the level of expression of said gene (s) of interest (i) by a set of epithelial cells of the scalp of a subject affected by a dandruff state or a subject or (ii) by epithelial cells cultured in vitro in the presence of one or more active agents whose known anti-dandruff activity, said compound or combination of compounds is selected when the value of the expression level measured in step c) of the above screening method is similar to said reference value. An expression rate value is similar to a reference value when the variation is less than .2 times the reference value, for example, is less than 1.5 times the reference value. The steps a) to d) of the above screening method can also be used to evaluate the effectiveness of a cosmetic or dermatological treatment with active agents presumed to prevent or treat a dandruff condition of the scalp. In these embodiments, the compound or combination of compounds to be tested consist of said assets presumed to prevent or treat a dandruff condition of the scalp. The present invention also relates to a method for determining the condition of the scalp of a subject comprising the steps of: a) providing a sample of epithelial cells obtained by sampling from the subject's scalp; b) measuring the rate expressing at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-D CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B., by the cells provided in step a), and c) comparing, for each of the genes tested, the level of expression measured in step b) with a reference value of said gene tested for a known state of the scalp.

The details of practical implementation of such a method have been described previously in the present description, as well as in the examples. In certain embodiments of the above method, the reference value is a level of expression of said gene (s) of interest by epithelial cells of a scalp not affected by a dandruff state or of a scalp for which a dandruff condition has been resolved. In these embodiments: (i) the absence of a film state is determined when the expression rate of said gene (s) measured in step b) is similar to the reference value, and ii) the occurrence of a film state is determined when the expression rate of said (said) gene (s) measured in step b) is greater than the reference value. In certain other embodiments of the above method, the reference value is a level of expression of said gene (s) of interest by epithelial cells of a scalp affected by a pellicular state. In these other embodiments: (i) the occurrence of a film state is determined when the expression rate of said gene (s) measured in step b) is similar to the reference value, and ii) the absence of a film state is determined when the expression rate of said gene (s) measured in step b) is lower than the reference value. According to yet another aspect, the present invention relates to methods for evaluating the effect of a cosmetic or dermatological treatment with an asset (s) presumed to prevent or treat a dandruff condition, comprising at least one step during which is determined, from epithelial cells that have been contacted with the active (s), the expression level of at least one gene selected from PSAPL genes I, CALML5, PLA2G2F , HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B, which is compared to a reference expression level value. The details of practical implementation of such a method have been described previously in the present description, as well as in the examples. In some embodiments of the above method, the reference value is a value of the level of expression of said gene (s) by epithelial cells of a scalp not affected by a dandruff state or a scalp for which a dandruff condition has been resolved. In these embodiments, said cosmetic or dermatological treatment is deemed active or effective when the value of the expression rate of said gene (s) of interest that is measured is similar to said reference value. In certain other embodiments, of the above method, reference value is the value of the level of expression of said gene (s) by epithelial cells of a scalp affected by a dandruff state. In these other embodiments, said cosmetic or dermatological treatment is deemed active or effective when the value of the expression rate of said gene (s) of interest that is measured is less than said reference value.

According to another aspect, the invention relates to a cosmetic or non-therapeutic process, in particular in vitro or ex vivo, for characterizing the effectiveness of a cosmetic treatment of the scalp, and preferably a treatment of the scalp. abnormal desquamation of the scalp, and preferably a dandruff condition of the scalp in an individual in need thereof, comprising at least the steps of: a) performing, prior to carrying out the cosmetic treatment, in a first sample of isolated skin, and preferably isolated scalp, taken from said individual, at least a first measurement of the level of expression of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAPI9-5, KRTAP7-1, and GPR109B, b) perform, after the cosmetic treatment is performed, in a second isolated skin sample, and preferably an isolated scalp, taken from said individual, at least one second measurement of the expression level of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, 111, AD CCL22, ADM, LYZ, P12, KRTAP19-5, TAP7-1, and GPR109B., and c) comparing the first and second measurements, in particular to derive information relating to an effect at least of the implementation of the cosmetic treatment. It goes without saying that the measurements made in steps a) and b) must be comparable to one another, and therefore be relative to the same parameter.

Preferably, a method of the invention makes it possible to demonstrate an effect of a cosmetic treatment capable of normalizing an abnormal or irregular desquamation of the scalp, and in particular a dandruff condition of the scalp. Still more preferably, a method of the invention makes it possible to characterize the effectiveness of a cosmetic treatment, and in particular a treatment of a dandruff condition of the scalp. Kits A bed suitable for use of the invention may comprise at least one collection of nucleic probes specifically hybridizing with an mRNA encoded by a gene selected from PSAPL1, CALML5, PLA2G2F, CCL22, DM, LYZ, MMP12, KRTAP19-5, KRTAP7 -1, and GPR109B. Preferably, the above nucleic probes are immobilized in an ordered manner on a suitable support, for example in the form of a matrix of nucleic acid probes whose nucleotide sequences and the respective locations, on the appropriate support surface, are known. Preferably, said kit comprises, as nucleic probes, exclusively nucleic probes specifically hybridizing with an mRNA encoded by a gene chosen from PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, I1212, KRTAP19. -5, KRTAP7-1, and GPR10913, which can be combined with additional nucleic probes hybridizing to one or more reference genes whose transcription rate does not vary with the dandruff condition of the scalp. Said additional probes are preferably chosen from nucleic probes hybridizing with the mRNAs resulting from the transcription of a gene constitutively expressed and constant by the cells ("housekeeping" gene or "housekeeping genes"), which includes the genes whose expression is required for the basic function of cells. Domestic genes include (i) genes encoding transcription factors, (ii) genes encoding repressors, (iii) genes encoding splice factors, (iv) genes encoding transcription factors, (v) ) genes encoding tRNA synthases, (vi) genes encoding RNA binding proteins, (vii) genes encoding ribosomal proteins, (viii) genes encoding RNA polymerase, (ix) genes encoding protein maturation factors, (x) genes encoding heat shock proteins, (xi) genes encoding histones, (xii) genes encoding cell cycle-acting proteins, (xiii) protein coding genes DNA replication or repair, (xiv) genes encoding proteins acting on carbohydrate metabolism, (xv) genes encoding citric acid cycle proteins, (xvi) genes encoding proteins acting on lipid metabolism, (xvi i) genes encoding proteins acting on amino acid metabolism, (xviii) genes encoding proteins acting on nucleotide synthesis, (xix) genes encoding proteins with NADH dehydrogenase activity, (xx) genes encoding Cytochrome C oxidases, (xxi) genes encoding mitochondrial proteins, (xxii) genes encoding lysosomal proteins, (xxiii) genes encoding proteosome proteins, and (xxiv) genes encoding cytoskeletal proteins. A kit suitable for the invention may further comprise an explanatory note 30 specifying the methods for determining a transcription level of an mRNA derived from the transcription of a gene selected from PSAPL1, CALML5, PLA2G2F, HLA-DRA. , CCL22, ADM, LYZ, M12, TAP19-5, KRTAP7-1, and GPR109B. In other embodiments, a kit suitable for use of the invention may comprise at least one antibody recognizing a protein encoded by a gene selected from PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM. , If appropriate, the antibody or antibodies are labeled with a detectable molecule, where appropriate, said kit also comprises antibodies, called second antibodies, antibody, recognizing the antibodies, or "first antibodies", directed against a protein encoded by a gene of interest, for example antibodies recognizing the Fc portion of said first antibodies, said second antibodies being labeled with a detectable molecule, for example a The present invention is further illustrated by, but is not limited to, the following examples: chromophore molecule, fluorophore molecule, or enzyme capable of catalyzing the transformation of a chromogenic substrate. [0009] A gene pool of a set of genes whose expression level is increased upon a reduction of a dandruff condition of the scalp. A. Materials and methods A.1. Clinical Study Protocol A clinical study was conducted in 60 male subjects with moderate to severe dandruff. Samples of epithelial cells of the scalp were taken at several times, and in particular before any anti-dandruff treatment (D1) and at the 56th day after the start of treatment with (0 is a placebo composition without dandruff active agent, (ii) or a composition comprising an anti-dandruff active (J57) As a placebo composition, a maltodextrin powder composition (100 maltodextrin) was used As a composition comprising an anti-dandruff active, a composition based on a probiotic, Lactobacillus was used. paracasei, and more specifically strain NCC-2461 The compositions are described in Table 1. Table 1 Test Protocol Compositions Ingredients Galenic Form Powder Excipient: Maltodextrin Galenic Form: Powder Active Dandruff Dandruff Composition Lactobacillus casei active agent 1x109 cfu of Lactabacillus paracasei NCC 2461 (ST11) (powder in sachet with r reconstitute in water, with a sachet containing 1x Lactabacillus paracasei cfu) Placebo composition Excipient: Maltodextrin. (powder in sachet to be reconstituted in water) Dosage: A treatment unit, ie a sachet of product diluted in water, to be taken once a day. For 56 days. Duration: Dose Ingested dose: 1 x 109 cfu of Lactabacillus paracasei NCC2461 (ST11) per day. Route of Administration: Oral5 A.2. Preparation of the samples to be analyzed The hair with their bulbs was taken from each of the subjects on day 1 and day 57. The isolation and purification of the RNA from pools of hair bulbs, as well as the validation of these RNA preparations (quantity, quality ...) was carried out beforehand. An analysis of the expression levels of a set of 28,869 human genes was then performed for selection of RNA samples on GeneChipfD Human Gene 1.0 ST chips marketed by Affymetrix. (United States). For this purpose, all the extracted RNA samples were hybridized on 24 Affymetrix Human Gene 1.0 ST chips. A3. Outcome Analysis Protocol Measurements of expression levels of the gene set in the samples of the subjects in the group treated with an active were compared with the expression levels of the same set of genes in the samples of the subjects of the placebo treated group. Global hybridization of extracted mRNAs with DNA probes immobilized on GenechiptD chips was verified to be of good quality. B. Results - Statistical analysis The statistical analysis was carried out according to a bifactorial plan, with a factor "treatment group" and a factor "time" (or treatment). In order to obtain, for both treatments, the list of differently expressed genes, a statistical analysis of variance (ANOVA) model was applied to the test results; which model takes into account the pairing by individuals (factor nested with the type of treatment) The results were, for each gene, for each individuals and for each treatment, a fold change value as well as for each treatment, an average fold change and a p-value. The p-values will be readjusted to take into account the "multitesting" effect. It is a bifactorial plan, with a factor "treatment group" and a factor "time" (or treatment). In order to have, for both treatments, the list of genes differently expressed a statistical model of analysis of variance (ANOVA) will be applied and will take into account the pairing by individuals (factor nested with the type of treatment). The result will be, for each gene, for each individual and for each treatment, a value of fold change as well as for each treatment, an average fold change and a p-value. The p-values will be readjusted to take into account the "multitesting" effect.

Contrasts were applied to compare the effect of anti-dandruff treatment versus placebo. The results show that, on samples of scalp epithelial cells taken from subjects in which the dermal state was greatly reduced or resolved, a significantly increased expression rate was measured, compared to the samples of the subjects receiving the placebo composition, for all the following genes PSAPL1, CAL5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, P12, KRTAPI9-5, KRTAP7-1, and GPR109B. The results of Example 1 show that the level of expression of each of the above genes constitutes a marker indicative of the dandruff condition of a scalp.

Claims (12)

REVENDICATIONS1. Use of the expression level of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-I, and GPR109B. an abnormal desquamation of the scalp, and preferably a dandruff condition of a scalp. 2. Use of the expression level of at least one gene chosen from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAPI9-5, KRTAP7-1, and GPR109B. screening assets to prevent and / or treat abnormal desquamation of the scalp, and preferably a dandruff condition of the scalp. 3. Use of the expression level of at least one gene chosen from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B., To determine the effect of a cosmetic treatment on anomalous desquamation of the scalp, and preferably a dandruff condition of the scalp. 4. Use according to any one of the preceding claims, characterized in that the expression level of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 of said genes is used. 5. Use according to any one of the preceding claims, characterized in that the level of expression consists of a transcription rate of the genes under consideration. 6. Use according to one of claims 1 to 4, characterized in that the expression rate consists of a production rate of the proteins encoded by the genes in question. 7. A method of screening for active agents to prevent and / or treat anomalous desquamation of the scalp, and preferably a dandruff condition of the scalp, comprising the steps of: a) providing cells capable of expressing at least one selected from the genes PSAPL1, CALML5, PLA2G2F, ELA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B. b) contacting said cells with a test compound, or C) measuring the level of expression of at least one gene selected from the genes specified for step a), d) comparing, for each of the genes tested, the level of expression measured at step c) with a reference value of said gene tested. 8. Process according to claim 7, characterized in that it comprises the following additional step: e) selecting said compound, or said combination of compounds, when the level of expression measured in step c) is respectively greater than a reference value for cells incubated in the absence of test compound. 9. Method according to one of claims 7 and 8, characterized in that the cells provided in step a) are selected from (i) epithelial cells obtained by sampling from the scalp, and (ii) a line epithelial cells. A method for determining the condition of the scalp of a subject comprising the steps of: a) providing a sample of epithelial cells obtained by sampling from the subject's scalp; b) measuring the expression rate of a subject; at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B., by the cells provided in step a), and c) comparing, for each of the genes tested, the level of expression measured in step b) with a reference value of said gene tested for a known state of the scalp. 11. A method for evaluating the effect of a cosmetic or dermatological treatment with an asset (s) presumed to prevent or treat an abnormal desquamation of the leather. hair, and preferably a dandruff condition of the scalp, comprising at least one step in which is determined, from epithelial cells that have been contacted with the active (s), the rate of expression of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B. which is compared with a value of reference expression. 25 12. Cosmetic or non-therapeutic process, in particular in vitro or ex vivo, to characterize the effectiveness of a cosmetic treatment of the scalp, and preferably a treatment of abnormal desquamation of the scalp, and preferably dermal state of the scalp in an individual in need thereof, comprising at least the steps of: a) performing, prior to performing the cosmetic treatment, in a first isolated skin sample, and preferably isolated scalp , taken from said individual, at least a first measurement of the level of expression of at least one gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7 -1, and GPR109B., B) perform, after carrying out the cosmetic treatment, in a second sample of isolated skin, and preferably isolated scalp, taken from said individual, at least a second measurement of the level of expression of at least a gene selected from the genes PSAPL1, CALML5, PLA2G2F, HLA-DRA, CCL22, ADM, LYZ, MMP12, KRTAP19-5, KRTAP7-1, and GPR109B., and c) comparing the first and second measurements, in particular in order to to deduce information relating to an effect at least of the implementation of the cosmetic treatment.