KR101868058B1

KR101868058B1 - Novel use of erythroid differentiation regulator 1 for skin regenerating or wound healing

Info

Publication number: KR101868058B1
Application number: KR1020160034323A
Authority: KR
Inventors: 조대호
Original assignee: 숙명여자대학교산학협력단
Priority date: 2016-03-23
Filing date: 2016-03-23
Publication date: 2018-06-18
Also published as: KR20170110745A

Abstract

The present invention relates to a novel use of erythroid differentiation regulator 1 for skin regeneration or wound healing. In the present invention, by treating the polypeptide, not only the migration ability and collagen production amount of the epithelial cells or fibroblasts were remarkably increased, but also the excellent wound healing effect in the acute wound animal model was confirmed, Or as an effective substance that can replace the preparation for wound healing.

Description

[0001] The present invention relates to a novel use of erythroid differentiation regulator 1 for skin regeneration or wound healing,

The present invention relates to a novel use of erythroid differentiation regulator 1 for skin regeneration or wound healing.

Skin is the primary protective membrane of the human body. It protects the internal organs of the body from irritation caused by external environment such as temperature, humidity change, ultraviolet rays, pollutants, and plays an important role in keeping the body homeostatic such as body temperature control. The keratin, which is located at the outermost part of the skin, is a tissue formed by a change in the cells of the skin, and consists of dead cells. In the dermal connective tissue of the dermis, the dermally formed cell layer rises to the epidermis and the cells lose their viability and become a firm and regular cell layer. The skin with this structure protects the moisture of our body from the outermost and acts as a defensive line to defend the various substances from outside. That is, when the skin surface is scratched, the rapid regeneration ability of the epidermis promotes the recovery of the wound, thereby preventing further infection through the wound and reducing the scarring on the skin surface.

When the damaged skin tissue is reconstructed, various reactions are involved. Specifically, the movement, proliferation, differentiation of keratinocytes, dislodgement of damaged cells, and production of the epithelial tissue are involved. The process of wound healing is a very complicated reaction involving various cells and factors. Platelet aggregation occurs at the wound site, and various cell proliferation factors such as a transforming growth factor, a platelet-derived proliferation factor, and an epithelial cell proliferation factor are liberated Stimulates cell proliferation by stimulating endothelial cells, vascular endothelial cells, phagocytic cells, fibroblasts, and epithelial cells. At the same time, these cells themselves produce and release substances such as fibroblast proliferation, transforming growth factor and interleukin The mechanism of wound healing proceeds.

Currently, EGF (epidermal growth factor), which is widely used as a wound healing agent because of its various activities, is either obtained by purification or obtained by overexpression in bacteria. It takes a lot of time, money, and labor to obtain by direct purification. Also, the over-expression method in bacteria has a problem that the recovery yield is very low due to low amount of cells in the cell and protease of bacteria. In addition, EGF has been reported to exhibit a low therapeutic effect on chronic wound sites, and it has been difficult to commercialize EGF due to the high price of efficiency due to short half-life due to temperature and proteolytic enzymes.

Under these circumstances, there is a need to develop a novel therapeutic agent having an effective therapeutic effect while minimizing the problems of conventional skin regeneration or wound healing agents, and studies have been made actively (Korean Patent Publication No. 2015-0135743) , Yet it is not enough.

DISCLOSURE OF THE INVENTION The present invention has been made in order to solve the above problems, and the present inventors have made intensive studies on a skin regeneration or wound treatment agent, and found that when treated with erythroid differentiation regulator 1, Or the fibroblast migration ability and the amount of collagen production are remarkably increased. On the basis thereof, the present invention has been completed.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for skin regeneration or wound healing, which contains, as an active ingredient, an erythropoiesis regulatory factor 1 polypeptide or a polynucleotide encoding the same.

Another object of the present invention is to provide a cosmetic composition for skin aging or wound healing, which comprises an erythropoietin regulatory factor 1 polypeptide as an active ingredient.

Still another object of the present invention is to provide a health functional food composition for improving skin aging or wounds, which comprises an erythropoiesis regulatory factor 1 polypeptide as an active ingredient.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for skin regeneration or wound healing, comprising an erythroid differentiation regulator 1 polypeptide or a polynucleotide encoding the same, as an active ingredient .

In one embodiment of the present invention, the N- or C-terminal of the polypeptide is an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, and a polyethylene glycol (PEG) &Lt; / RTI >

In another embodiment of the present invention, the polypeptide of the present invention may be contained at a concentration of 100 to 3000 ng / mL.

In another embodiment of the present invention, the wound may be wound.

In another embodiment of the present invention, the composition may further comprise a pharmaceutically acceptable carrier.

Further, the present invention provides a health functional food / cosmetic composition for skin aging or wound healing, which comprises an erythropoiesis regulatory factor 1 polypeptide as an active ingredient.

In another embodiment of the present invention, the composition may be in the form of a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a wax or a spray.

The present invention also provides a skin regeneration or wound treatment method comprising the step of administering the polypeptide to a subject.

The present invention also provides a skin regeneration or wound treatment use of the erythropoiesis regulatory factor 1 polypeptide.

The composition according to the present invention contains an erythroid differentiation regulator 1 polypeptide as an active ingredient and when the polypeptide is treated, the ability of epithelial cells or fibroblasts to move and collagen production is remarkably increased In addition, the excellent wound healing effect in an acute wound animal model can be confirmed, and it is expected that it can be used as an effective substance that can replace the existing skin regeneration or wound treatment formulations.

FIG. 1A shows the results of evaluating the ability of HaCaT cell line to migrate by ERDR1 treatment through a Scratch assay.
FIG. 1B shows the result of evaluating the migration ability of the HaCaT cell line according to ERDR1 treatment.
FIG. 2A shows the results of evaluating the ability of human fibroblasts to migrate by ERDR1 treatment through the Transwell migration assay.
Fig. 2B is a result obtained by evaluating the migration ability of human fibroblasts by the ERDR1 treatment.
FIG. 3A shows the results of real-time PCR analysis of collagen 1A1, 1A2, 3A1 mRNA expression of human fibroblasts by ERDR1 treatment.
FIG. 3B shows the result of evaluation of collagen protein production of human fibroblasts by ERDR1 treatment through sircol assay.
Fig. 4A shows the results of confirming the size change of the wound area according to the ERDR1 treatment in the acute wound animal model. Fig.
Fig. 4B shows the result of skin regeneration effect of ERDR1 treatment in tissue of an acute wound animal animal through tissue staining.

Hereinafter, the present invention will be described in detail.

The present invention relates to a pharmaceutical composition for the treatment of skin regeneration or wound healing, comprising an erythroid differentiation regulator 1 polypeptide or a polynucleotide encoding the same as an active ingredient; The use of erythropoiesis regulator 1 polypeptides for skin regeneration or wound healing; And administering a therapeutically effective amount of the polypeptide to the subject.

The Erythroid Differentiation Regulator 1 polypeptide of the present invention is the first protein found in mouse leukemia cell lines and is known to be released from cells under stress conditions. However, it has not been known about skin regeneration or wound healing to be. The polypeptide may be composed of the amino acid sequence shown in SEQ ID NO: 1, and preferably has at least 75%, preferably at least 80%, more preferably at least 90%, and most preferably at least 75% And may additionally comprise amino acid sequences having a homology of at least 95% with respect to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: .

The present invention may also include functional variants of Erythroid differentiation regulator 1 polypeptide. Such functional variants include biological equivalents of the erythropoiesis regulatory factor 1 sequences described herein. For example, additional changes can be made to the amino acid or polynucleotide sequence of the polypeptide to further improve the binding affinity and / or other biological properties of the polypeptide. Such modifications include deletion of the amino acid sequence residues of the antibody. Insertion, and / or substitution, and are based on the relative similarity of amino acid side chain substituents, such as hydrophobicity, hydrophilicity, charge size, and the like. By analysis of the size, shape and type of amino acid side chain substituents, arginine, lysine and histidine are both positively charged residues; Alanine, glycine and serine have similar sizes; Phenylalanine, tryptophan and tyrosine have similar shapes. Based on these considerations, therefore, arginine, lysine and histidine; Alanine, glycine and serine; And phenylalanine, tryptophan and tyrosine are biologically functional equivalents.

In addition, the polypeptides of the present invention can be obtained by a variety of methods well known in the art. As an example, it can be produced by polynucleotide recombination and protein expression system, by synthesis in vitro through chemical synthesis such as polypeptide synthesis, and by cell-free protein synthesis.

Also, to obtain better chemical stability, enhanced pharmacological properties (half-life, absorbency, potency, efficacy, etc.), altered specificity (e.g., broad biological activity spectrum), reduced antigenicity, A protecting group may be bonded at the C-terminus. Preferably, the protecting group may be an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group or a polyethylene glycol (PEG), but the modification of the polypeptide, Any ingredient that can be promoted can be included without limitation. As used herein, the term "stability" also refers to the storage stability (e.g., room temperature storage stability) as well as the in vivo stability that protects the polypeptide of the present invention from attack by a protein cleaving enzyme in vivo.

In the present invention, " polynucleotide " is a polymer to which a nucleotide is bonded, and serves to transmit genetic information. For the purpose of the present invention, the polynucleotide of SEQ ID NO: 1 encodes the polypeptide of SEQ ID NO: 1, and the polynucleotide of SEQ ID NO: 2 is at least 75%, preferably at least 85% May comprise a sequence having 90% or more, and most preferably 95% or more sequence homology. As used herein, the term "homology" is intended to indicate a degree of similarity to a wild-type amino acid sequence or a polynucleotide sequence. Such homology comparison can be performed using a comparison program well known in the art, The same sex can be calculated as a percentage (%).

Alternatively, the polypeptides of the present invention or polynucleotides encoding them can be delivered to a pharmaceutically acceptable carrier such as a colloidal suspension, powder, saline, lipid, liposome, microspheres, or nanospheric particles. They may be associated with or associated with carriers and may be in the form of lipids, liposomes, microparticles, gold, nanoparticles, polymers, condensation reagents, polysaccharides, polyamino acids, dendrimers, saponins, And can be delivered in vivo using known delivery systems.

In addition, pharmaceutically acceptable carriers may be formulated with pharmaceutically acceptable carriers such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, But are not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, in addition to the above components, a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like may be further included.

As used herein, the term "treatment" refers to any action that improves or alters the symptoms of a wound by administering a pharmaceutical composition according to the present invention.

In the present invention, "individual" means a subject in need of treatment for a wound, and more specifically refers to a mammal such as a primate, a mouse, a dog, a cat, a horse and a cow, which are human or non-human.

As used herein, the term "skin regeneration " refers to a series of reactions in which skin tissue is reconstituted in response to overall skin aging and skin-induced wounds, thereby exhibiting skin elasticity and wrinkle-reducing effects. On the other hand, the wound may preferably be wound, but is not limited thereto.

According to one embodiment of the present invention, by treating the erythropoietin regulatory factor 1 polypeptide, it is possible to improve not only the migration ability of the human epithelial cell line and fibroblast cell, which is an essential step for wound healing, but also the collagen production amount, (See Examples 2 to 3), an excellent wound healing effect could be confirmed using an acute wound animal model (see Example 4), and an existing skin regeneration or wound treatment agent could be replaced Which can be used as an effective substance.

For the purpose of the present invention, the pharmaceutical composition of the present invention may contain 100-3000 ng / mL of erythropoiesis regulatory factor 1 polypeptide preferably for the skin regeneration effect, The concentrations that can be expected are not limited thereto.

The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intramuscularly, intravenously, intraperitoneally, subcutaneously, intradermally, or topically) depending on the intended method, The severity and severity of the disease, the form of the drug, the route of administration and the time of administration, may be appropriately selected by those skilled in the art.

In particular, when the pharmaceutical composition of the present invention is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, Surfactant, water, ionic emulsifier, nonionic emulsifier, filler, sequestering agent, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent, And any other ingredients conventionally used in dermatologic external preparations, such as, for example, cosmetics, cosmetics, and the like. The components can also be introduced in amounts commonly used in the field of dermatology. In addition, when the pharmaceutical composition is provided as an external preparation for skin, it may be a formulation such as, but not limited to, ointment, patch, gel, cream or spray.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered simultaneously, separately or sequentially with conventional therapeutic agents, and may be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, body weight, absorbency of the active ingredient, inactivity, excretion rate, disease type, The severity of obesity, sex, weight, age, and the like.

In another aspect of the present invention, the present invention provides a health functional food / cosmetic composition for skin aging or wound healing, which comprises the polypeptide or the polynucleotide encoding the polypeptide as an active ingredient.

As used herein, the term "improvement" means any action that at least reduces the degree of symptom associated with the condition being treated. At this time, the health functional food / cosmetic composition may be used simultaneously with or separately from the medicament for treatment before or after the onset of the disease for prevention or improvement of skin aging or wound.

In the health functional food composition of the present invention, the active ingredient can be directly added to the food or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). In general, the composition of the present invention may be added in an amount of preferably not more than 15% by weight, preferably not more than 10% by weight, based on the raw material. However, in the case of long-term ingestion intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range.

The health functional food composition of the present invention may contain other ingredients as essential ingredients other than those containing the above-mentioned effective ingredients. For example, various flavoring agents or natural carbohydrates may be added as an additional ingredient, such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. (Such as taurine, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (such as saccharin and aspartame) are advantageously used as flavorings other than those described above . The ratio of the natural carbohydrate can be appropriately determined by a person skilled in the art.

In addition to the above, the health functional food composition of the present invention can be used as a nutritional supplement, a vitamin, a mineral (electrolyte), a flavoring agent such as a synthetic flavoring agent and a natural flavoring agent, a coloring agent and a thickening agent (cheese, chocolate, Alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks and the like. These components can be used independently or in combination, and the proportion of such additives can also be appropriately selected by those skilled in the art.

The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.

An effective carrier contained in the cosmetic composition of the present invention may be a carrier conventionally used in the art depending on the formulation. When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.

The ingredients contained in the cosmetic composition of the present invention include, in addition to the active ingredient and the carrier ingredient, the ingredients conventionally used in cosmetic compositions and include conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, .

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.

[ Example ]

Example 1. Human Epithelial cell line Mobile ability evaluation

Migration of epithelial cells is one of the essential processes for wound healing. In this embodiment, the ability of HaCaT, a human epithelial cell line, to undergo ERDR1 treatment was evaluated by Scratch assay. After generation of the scratch, cell migration to the scratch site according to the passage of time (6, 12, 18 h) was observed and quantified and evaluated. On the other hand, as a control group, scratch was generated and a group without additional treatment was used.

As a result, as shown in Fig. 1, in the control group, cells did not migrate to the scratch site in spite of the passage of time, whereas in the ERDR1-treated group, many cells migrated to the scratch site (Fig. , Especially after 18 hours of treatment with ERDR1, the cells were found to be present in about 85% of the entire area of the scratch (see FIG. 1B). From the above results, it can be seen that ERDR1 promotes the migration of epithelial cells, one of the wound healing processes.

Example 2. Human fibroblast Mobile ability And collagen Generation evaluation

Fibroblast migration is one of the essential processes for wound healing. In this process, the production of extracellular matrix (ECM) and collagen play a very important role in the formation of environment that promotes wound healing. In this example, transwell migration assay was performed to evaluate the ability of human fibroblast (HDF) to migrate according to ERDR1 treatment (500, 1000, 2000 ng / ml) and real time PCR and sircol assay We investigated collagen 1A1, 1A2, 3A1 mRNA and collagen protein production of human fibroblasts according to ERDR1 treatment (100, 500, 1000, 2000 ng / ml).

As a result, as shown in FIG. 2, in the group treated with ERDR1, cell migration was promoted and a number of cells were observed (see FIG. 2A), and the cell migration promoting effect tended to be dependent on ERDR1 concentration Reference). In addition, as shown in Fig. 3, the collagen 1A1, 1A2, and 3A1 mRNAs were significantly increased in the group treated with ERDR1, particularly, the group treated with 500ng / ml or more (see Fig. 3a) Was greatly increased by the processing of ERDR1 (see FIG. 3B). From the above results, it was found that ERDR1 induces fibroblast migration and collagen production and contributes to promoting wound healing.

Example 3. Acute wound Evaluation of wound healing effects in animal models

Based on the results of Examples 1 and 2, in this Example, an attempt was made to confirm the wound healing effect of ERDR1 using an acute wound animal model. Specifically, 6-week-old BALB / c nude mice (Oriental Bio) were adapted for 1 week and 12-mm wounds were applied to seven-week-old Balb / c nude mice to establish an acute wound model. Then, ERDR1 was applied to the wound site every 5 days from the wound creation date (D0), and the wound area was measured and photographed at intervals of 2 days. By performing tissue staining on the 6th day, wound healing Effect was observed. On the other hand, a vehicle control group (PBS) was used as a control group.

As a result, as shown in FIG. 4, in the control group, natural wound closure was observed at the 12th day from the wound creation day, whereas wound healing was faster at 10 days in the ERDR1 treated group than in the control group (See FIG. 4A). Similarly, in the result of tissue staining, it was also found that many skin tissues and hair follicles at the wound area were formed and skin regeneration was progressing actively (see FIG. 4B).

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

<110> Industry-Academic Cooperation Foundation, Sookmyoung Woman's University <120> Novel use of erythroid differentiation regulator 1 for skin regenerating or wound healing <130> P16U10C0629 <160> 2 <170> KoPatentin 3.0 <210> 1 <211> 177 <212> PRT <213> Erythroid differentiation regulator 1 polypeptide <400> 1 Met Pro Thr Gly Arg Thr Asp Gly Arg Thr His Gly Arg Thr Pro Gln 1 5 10 15 Gly Arg Lys Pro Ala Pro Thr Ala Pro Leu His Pro Pro Gln His Thr 20 25 30 Gly His Thr Arg Ala Pro Arg Pro Pro Arg His Thr Arg His Thr Arg 35 40 45 His Thr Arg Gln Ala Gly Gln Ala His Ala Ser Ala Gly Pro Ala Ala 50 55 60 Pro Ala Thr Gln Thr Arg Thr Ser Arg Arg Gly Gln Asp Val His Pro 65 70 75 80 Pro Arg Ser Ser Cys Met Cys His Arg Pro Ser Pro Arg Trp Thr Asp 85 90 95 Gly Arg Thr His Ala Arg Arg Gln Arg Pro Pro Val Thr Ala Ala Ala 100 105 110 His Ser Asp Val Thr His Glu Ser Thr His Val Glu Ala Asp Ala Val 115 120 125 Val Lys Met Ser Leu Pro Ser Pro Gln Asp Gly Arg Thr Asp Ser Thr 130 135 140 Arg Cys Ala Cys Arg Arg Gly Arg Gln Asp Gly Ala Ile Leu Thr Glu 145 150 155 160 Glu Gly Ala Arg Gln Gln Gly Leu Thr Ala Tyr Arg Asn Ala Pro Pro 165 170 175 Gln <210> 2 <211> 801 <212> DNA <213> Erythroid differentiation regulator 1 polynucleotide <400> 2 gtccgttctc ttttagccgc agctatggtt tctgccctaa ttattcttgt ccttatttgt 60 aatttaattc ttaatttaat ttaatttata attttgttgt aagtttctct gtgggcgtga 120 atggaaagtc taacccgtgt ttctctgttc agcgtccgcc ggtcacggcc gccgccccca 180 gcgacgtcac ccacacgcgc agaagcggac gccgcggtca agatgtctct gccatgccca 240 cgggacgcac ggacggacgg acgcacggac ggactccaca aggtaggaag cctgcgccga 300 ccgcaccgct gcacccacca cagcacacag gacacacgcg ggccccgcgc ccgcccaggc 360 acacgcggca cacacggcac acacggcagg caggccaggc acacgcatcc gcaggacccg 420 ccgcacccgc cacgcagaca cggacgagcc gccgcggtca agatgttcac ccgccgcggt 480 caagatgtat gtgccaccga ccctcgcccc gctggacgga cggacggacg cacgcacgcc 540 gtcagcgtcc accggtcact gccgccgccc acagtgatgt cacccacgaa agcacacacg 600 tagaagcgga cgccgtggtc aagatgtctc tgccatcccc acaggacgga cggacggact 660 ccacaaggtg cgcgtgtcgc cgaggccgcc aggacggagc gattctcacg gaggaaggag 720 cacgccaaca gggcctgact gcgtacagaa atgccccccc tcaataaaat tgcagttgaa 780 atggaaaaaa aaaaaaaaaa a 801

Claims

An erythroid differentiation regulator 1 comprising a polypeptide or a polynucleotide encoding the same as an active ingredient.

The method according to claim 1,
The N- or C-terminal end of the polypeptide may have a protecting group selected from the group consisting of an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, and polyethylene glycol (PEG) &Lt; / RTI > or a pharmaceutically acceptable salt thereof.

The method according to claim 1,
Wherein the polypeptide is contained at a concentration of 100 to 3000 ng / mL.

The method according to claim 1,
Wherein the wound is wound-healing.

The method according to claim 1,
Wherein said composition further comprises a pharmaceutically acceptable carrier.

An erythroid differentiation regulator (1) comprising a polypeptide as an active ingredient.

The method according to claim 6,
The N- or C-terminal end of the polypeptide may have a protecting group selected from the group consisting of an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, and polyethylene glycol (PEG) &Lt; / RTI >

The method according to claim 6,
Wherein the composition is in the form of a suspension, emulsion, paste, gel, cream, lotion, powder, wax or spray.