KR20230005514A - Composition for preveting or treating sepsis comprising DRG2 inducer - Google Patents

Abstract

The present invention relates to a composition for preventing or treating sepsis containing a DRG2 inducer, a method for selecting a substance for preventing or treating sepsis, and the like. The DRG2 inducer according to the present invention increases the expression level of the DRG2 gene or the activity of the DRG2 protein in the body, thereby effectively treating sepsis caused by microbial infection, as well as increasing sensitivity to existing sepsis treatment agents so that it is possible to significantly increase an effect of treating sepsis.

Description

Composition for preventing or treating sepsis comprising a DRG2 inducer

The present invention relates to a composition for preventing or treating sepsis containing a DRG2 inducer, a method for selecting a substance for preventing or treating sepsis, and the like.

Sepsis is a disease in which microorganisms rapidly proliferate in the blood caused by microbial infection, resulting in an abnormal defense of the body against infected microorganisms, i.e., complex interactions between the host's immune, inflammatory, and coagulation systems. is understood to occur. Such sepsis can potentially cause septic shock. When sepsis gets worse, the function of various organs (heart, kidneys, liver, brain, lungs, etc.) deteriorates, and when it gets worse, a state of shock occurs. Sepsis can be caused by a variety of pathogens, the most common being bacteria, but it can also be caused by viruses or fungi. There are pneumonia that causes lung infection, urinary tract infection that causes bladder and kidney infection, cellulitis that occurs in the skin, appendicitis that occurs in the abdomen, or meningitis that occurs in the brain. Damage to the heart, liver, lungs, or kidneys occurs, and in severe cases, about 20 to 50% of patients die from septic shock. In addition, sepsis may occur due to infection after surgery, and sepsis as a hyperacute inflammatory reaction caused by infection after surgery leads to death in 40 to 90%.

In order to treat such sepsis, many attempts have been made to use antagonists for TNF-α, IL-1β, IL-6, etc. as therapeutic agents for the purpose of suppressing inflammatory responses, but most have failed, and mechanical ventilation treatment and active protein C administration have been attempted. Although various methods such as glucocorticoid treatment have been tried, no clear treatment has been developed yet.

Therefore, if an effective treatment for sepsis is developed, it is expected that the high mortality rate due to sepsis can be significantly reduced.

Domestic Patent Publication 10-2021-0061217

The present invention has been made to solve the above problems in the prior art, and an object of the present invention is to provide a composition for preventing or treating sepsis containing a DRG2 inducer as an active ingredient.

In addition, a) processing a candidate substance to cells containing DRG2 (Developmentally-regulated GTP-binding protein 2) gene or DRG2 protein; b) measuring the expression level of the DRG2 gene or the activity of the DRG2 protein; and c) classifying as a substance for preventing or treating sepsis when the expression level of the DRG2 gene or the activity of the DRG2 protein is increased. The purpose.

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

The present invention provides a pharmaceutical composition for preventing or treating sepsis comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient.

In one embodiment of the present invention, the inducer may preferably be a DRG2 gene expression promoter or a DRG2 protein activator, and the expression promoter refers to a substance that promotes the expression of the DRG2 gene, and the activator may be a DRG2 gene expression promoter. A substance that increases the activity of a protein. More preferably, it may include biomolecular substances such as nucleic acids, peptides, aptamers, proteins, compounds, natural products, natural extracts, lipids, and complexes thereof. The mechanism of the expression promoter or activator is not particularly limited, but may be, for example, to increase gene expression, such as transcription or translation.

In another embodiment of the present invention, the inducer is preferably a DRG2 protein; Alternatively, it may be an expression vector containing a polynucleotide encoding the DRG2 protein. More preferably, the DRG2 protein is a protein comprising the amino acid sequence represented by SEQ ID NO: 1, and the polynucleotide is a protein comprising the base sequence represented by SEQ ID NO: 2. It may be a polynucleotide comprising the sequence.

In another embodiment of the present invention, the sepsis may be sepsis or septic shock.

In addition, the present invention a) DRG2 (Developmentally-regulated GTP-binding protein 2) gene or the step of processing a candidate material to cells containing the DRG2 protein; b) measuring the expression level of the DRG2 gene or the activity of the DRG2 protein; and c) classifying the substance as a substance for preventing or treating sepsis when the expression level of the DRG2 gene or the activity of the DRG2 protein is increased.

In one embodiment of the present invention, the step of measuring the expression level of the DRG2 gene or the activity of the DRG2 protein is preferably a reverse transcriptase-polymerase chain reaction (reverse transcriptase-polymerase chain reaction), real-time polymerase chain reaction (real time) -polymerase chain reaction), western blotting, northern blotting, ELISA (enzyme linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, immunoprecipitation assay, and immunohistochemical analysis It can be measured by any one or more methods selected from the group consisting of (immunohistochemical analysis), but is not limited thereto, but is a method known to measure the expression level of a gene or the activity of a protein.

In another embodiment of the present invention, the candidate material may preferably include biomolecular materials such as nucleic acids, peptides, aptamers, proteins, compounds, natural products, natural extracts, lipids, and complexes thereof, but DRG2 It is not limited thereto as long as it is a substance capable of suppressing the expression of a gene or the activity of a DRG2 protein.

In addition, the present invention provides a food composition for preventing or improving sepsis comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient.

In addition, the present invention provides a feed additive for preventing or improving sepsis comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient.

In addition, the present invention provides a composition for preventing or treating sepsis comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer and a septic agent as active ingredients.

In addition, the present invention provides a method for preventing or treating sepsis comprising administering to a subject a composition containing a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient.

In addition, the present invention provides a preventive or therapeutic use of a composition comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient.

The DRG2 inducer according to the present invention not only can effectively treat sepsis caused by microbial infection by increasing the expression level of DRG2 gene or the activity of DRG2 protein in the body, but also increases the sensitivity to existing sepsis drugs, thereby increasing the sepsis treatment effect. can be significantly increased. Therefore, it is possible to significantly lower the mortality rate due to sepsis, septic shock, etc., and in particular, it can effectively act on patients with reduced immunity such as after surgery or chemotherapy, thereby significantly increasing the effect of surgery and treatment in various fields. It is expected to be widely applicable to

Figure 1 is a graph showing the results of confirming the survival rate in sepsis of wild-type mice and DRG2 knockout mice according to an embodiment of the present invention.
Figure 2 is a graph showing the results of measuring the change in body weight during sepsis infection of wild-type mice and DRG2 knockout mice according to an embodiment of the present invention.

In the present invention, the DRG2 inducer, that is, by increasing the expression level of the DRG2 gene in the body or by increasing the activity of the DRG2 protein, can effectively prevent and treat sepsis induced by microbial infection, as well as a previously used sepsis treatment. The therapeutic effect can be remarkably enhanced through combined administration with

In the present specification, "sepsis" is a general meaning including all diseases caused by infection with microorganisms, such as sepsis and septic shock. “Amelioration, prevention, or treatment of sepsis or septic shock” means clinical symptoms associated with sepsis and conditions associated with multi-organ dysfunction syndrome (e.g., fever of various degrees, hypoxemia, death, tachycardia, endothelitis, myocardial infarction) means the reduction, amelioration, delay or elimination of all or some of the symptoms of hypercongestion, altered mental state, vascular collapse and organ damage, acute respiratory distress syndrome, coagulopathy, heart failure, renal failure, shock, or coma, etc.) do. The microorganisms may be caused by bacteria, but also sepsis caused by viruses or fungi, and examples thereof include Vibrio, streptococcus, staphylococcus, Escherichia coli, pneumonia, Pseudomonas aeruginosa, fungi, and Klebsiella, but sepsis in the body. It is not limited thereto as long as it is a microorganism known to induce.

DRG (Developmentally-regulated GTP-binding protein) of the present invention is a protein involved in various intracellular regulation and is known to form a large superfamily. In this superfamily, there are three important subfamilies, such as trimeric G protein (e.g. transducin), monomeric G protein (e.g. ras), and GTPase involved in protein synthesis (e.g. elongation factor Tu). A new group of G proteins has been discovered, and DRG has all five regions from G1 to G5 required for binding to GTP, and is known to be similar in size to trimeric G protein. However, it is classified as a new subfamily because its amino acid sequence has completely different characteristics from not only the trimeric G protein but also the existing G protein subfamilies. In addition, DRG includes DRG1 and DRG2, which are known to be present in almost all types of cells, from bacteria to humans.

In the present specification, "DRG2" may include functional homologues having amino acid homology of 90% or more and the same protein activity as well as the wild type protein. Those skilled in the art will readily understand that, as long as 90% or more homology is maintained by such artificial modification and the same activity as the DRG2 wild-type protein is maintained, it is an equivalent protein. Therefore, the DRG2 protein according to the present invention may include amino acid sequence variants thereof as long as they have the same protein activity as the wild type. Here, the variant refers to a protein having a sequence different from the natural amino acid sequence by deletion, insertion, non-conservative or conservative substitution of one or more amino acid residues, or a combination thereof. Such variants may include functional homologues with substantially equivalent activity to wild-type proteins or proteins with modifications that increase or decrease physicochemical properties. Preferably, it is a variant in which the physical and chemical properties of the protein are modified. For example, physical factors such as temperature, moisture, pH, electrolyte, reducing sugar, pressurization, drying, freezing, interfacial tension, light, repeated freezing and thawing, high concentration conditions, acid, alkali, neutral salt, organic solvent, metal ion It is a variant with increased structural stability against the external environment of chemical factors such as , redox agents and proteases. In addition, it may be a mutant in which enzyme activity is increased due to a mutation in the amino acid sequence.

In the present specification, “DRG2 inducer” refers to all substances that can increase the expression of the DRG2 gene or increase the activity of the DRG2 protein, and for example, the DRG2 protein itself or the DRG2 It may also be in the form of an expression vector to which the encoding polynucleotide is operably linked. The expression vector preferably refers to a plasmid, phage, cosmid, viral vector or other medium known in the art. Viral vectors may include, for example, retrovirus, adenovirus, adenovirus-associated virus, herpes virus, and avipoxvirus. And the polynucleotide encoding DRG2 is characterized in that it is represented by SEQ ID NO: 2, but is not limited thereto, and has an identity of 70% or more, preferably 80% or more, more preferably 90% or more of the nucleotide sequence of SEQ ID NO: 2. It may be a nucleotide sequence having the same identity.

In the present specification, "individual" refers to a subject to which the composition of the present invention can be administered, preferably a mammal, but the subject is not limited.

In the present specification, “pharmaceutical composition” may be in the form of capsules, tablets, granules, injections, ointments, powders, or beverages, and the pharmaceutical composition may be intended for humans. can The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavors, etc. for oral administration, and buffers, preservatives, and painless agents for injections. A topical, solubilizing agent, isotonic agent, stabilizer, etc. may be mixed and used, and in the case of topical administration, a base, excipient, lubricant, preservative, etc. may be used. Formulations of the pharmaceutical composition of the present invention may be variously prepared by mixing with the pharmaceutically acceptable carrier as described above. For example, for oral administration, it can be prepared in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and in the case of injections, it can be prepared in unit dosage ampoules or multiple dosage forms. there is. In addition, dragees, gels, pills, powders, granules, suppositories, external preparations, solutions, suspensions, sustained-release preparations, slurries, etc. may be formulated and used. On the other hand, examples of carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like may be further included.

The route of administration of the pharmaceutical composition according to the present invention is not limited thereto, but oral or parenteral administration is preferred, for example, oral, intravenous, intramuscular, intraarticular, synovial, intraarterial, intramedullary, These include intrathecal, intracardiac, transdermal, intradermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual, rectal, intrasternal, intralesional, intracranial, and the like.

The dosage of the pharmaceutical composition of the present invention depends on the activity of the specific compound used, age, body weight, general health, sex, diet, administration time, route of administration, excretion rate, drug combination and severity of the specific disease to be prevented or treated. It can vary widely depending on factors, and varies depending on the patient's condition, weight, disease severity, drug form, administration route and period, but can be appropriately selected by a person skilled in the art, and 0.0001 to 500 mg/kg or 0.001 to 0.001 mg/kg per day. It can be administered at 500 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way.

In this specification, "food composition" can be used in various foods, for example, beverages, gum, tea, vitamin complexes, health supplements, etc., and can be used in pills, powders, granules, infusions, tablets, capsules or It can be used in beverage form. The food composition includes a health functional food composition. At this time, the amount of the DRG2 inducer in the food or beverage may be added at 0.01 to 30% by weight of the total food weight in the case of the food composition of the present invention, and 0.02 to 10g based on 100mL in the case of a health drink composition, preferably may be added at a rate of 0.3 to 1 g.

In the food composition of the present invention, as an essential component, there is no particular limitation on ingredients added other than the DRG2 inducer, and conventional food additives used in the art, such as natural carbohydrates, flavoring agents, flavoring agents, coloring agents, fillers, and stabilizers , various nutrients, vitamins, minerals (electrolytes), etc. may be included. Examples of the natural carbohydrate include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; polysaccharides such as dextrins, cyclodextrins; Conventional sugars such as the like and sugar alcohols such as xylitol, sorbitol, and erythritol may be used. Examples of the flavoring agents include natural flavoring agents (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. . Examples of flavoring agents include honey, D-mannitol, maltitol solution, and krill concentrate. In addition, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, a preferred embodiment is presented to aid understanding of the present invention. However, the following examples are provided to more easily understand the present invention, and the content of the present invention is not limited by the following examples.

[Example]

Example 1: Confirmation of the effect of DRG2 on sepsis

1.1. Confirmation of the survival rate of DRG2 knockout mice

In order to confirm the effect of DRG2 (Developmentally-regulated GTP-binding protein 2) on sepsis, the survival rate of mice in which sepsis was induced was firstly confirmed. More specifically, 10- to 12-week-old female mice, wild type (WT) mice and DRG2 knockout mice (DRG2 KO, Macrogen, Korea) were treated with LiCl, a GSK-3β (Glycogen synthase kinase kinase 3 beta) inhibitor, respectively. It was added to drinking water to a final 0.4 w/v% and provided for 10 days, and as a control, 0.4 w/v% NaCl was provided for 10 days. After 10 days, Listeria monocytogenes was diluted in 1X phosphate buffered saline (PBS), and then intraperitoneally injected into each mouse at a concentration of 5.5X10 ⁴ CFU/g to induce sepsis due to bacterial infection, and every 24 hours. Survival was confirmed. Afterwards, all experiments were repeated at least three times, and the results were expressed as mean values ± standard deviations. Statistical significance was confirmed by Student's t-test, and if P < 0.05, it was judged to be statistically significant. * indicates P < 0.05, ** indicates P < 0.01. The results are shown in Figure 1.

As shown in FIG. 1, it was confirmed that the survival rate of DRG2 knockout mice was reduced compared to wild-type mice given NaCl (FIG. 1B). In the case of wild-type mice pretreated with LiCl, 50% of mice survived up to 10 days, and it was confirmed that the survival rate significantly increased compared to wild-type mice treated with NaCl (FIG. 1D). On the other hand, it was confirmed that there was no significant difference in DRG2 knockout mice pretreated with LiCl (FIG. 1E). Through the above results, DRG2 plays an important role in increasing the survival rate in sepsis, and when GSK-3β, which affects the inflammatory response, is inhibited, the survival rate is increased in wild-type mice, but it has little effect on survival rate in DRG2 knockout mice. confirmed that That is, it was confirmed that DRG2 plays an important role in the survival rate in sepsis.

1.2. Check body weight change of DRG2 knockout mice

Sepsis was induced in the same manner as in Example 1.1, and body weight was measured every 24 hours. The results are shown in Figure 2.

As shown in FIG. 2 , both wild-type mice and DRG2 knockout mice showed a rapid weight loss in NaCl-treated mice (FIG. 2B). In the case of DRG2 knockout mice, they all died on the 3rd day, so their body weight could not be measured any more. In the case of wild-type mice pretreated with LiCl, the body weight decreased slightly at the beginning, but it was confirmed that the body weight recovered after the 6th day. Through this, when GSK-3β was inhibited, sepsis was cured in wild-type mice. It was confirmed that it was being recovered (Fig. 2C). On the other hand, DRG2 knockout mice pretreated with LiCl showed a similar weight loss as that of DRG2 knockout mice not pretreated with LiCl (FIG. 2E). Through the above results, it was confirmed that sepsis was not alleviated in DRG2 knockout mice even when GSK-3β was inhibited. It was confirmed that this result was consistent with the survival rate result.

Through the above results, the DRG2 gene and / or protein of the present invention plays a very important role in the treatment of sepsis caused by bacterial infection, and in the situation where the DRG2 gene is not expressed and the DRG2 protein is not produced, the DRG2 gene and / or protein is not produced. It was confirmed that the sensitivity was significantly reduced. Therefore, an inducer capable of increasing the expression or activity of the DRG2 protein can significantly increase the sepsis treatment effect, and the composition containing the DRG2 inducer of the present invention as an active ingredient is expected to be effectively used for the treatment of sepsis. .

The above description of the present invention is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

<110> University of Ulsan Foundation For Industry Cooperation RopheLBio Co., Ltd. <120> Composition for preveting or treating sepsis comprising DRG2 inducer <130> MP21-053 <160> 2 <170> KoPatentIn 3.0 <210> 1 <211> 364 <212> PRT <213> Homo sapiens <400> 1 Met Gly Ile Leu Glu Lys Ile Ser Glu Ile Glu Lys Glu Ile Ala Arg 1 5 10 15 Thr Gln Lys Asn Lys Ala Thr Glu Tyr His Leu Gly Leu Leu Lys Ala 20 25 30 Lys Leu Ala Lys Tyr Arg Ala Gln Leu Leu Glu Pro Ser Lys Ser Ala 35 40 45 Ser Ser Lys Gly Glu Gly Phe Asp Val Met Lys Ser Gly Asp Ala Arg 50 55 60 Val Ala Leu Ile Gly Phe Pro Ser Val Gly Lys Ser Thr Phe Leu Ser 65 70 75 80 Leu Met Thr Ser Thr Ala Ser Glu Ala Ala Ser Tyr Glu Phe Thr Thr 85 90 95 Leu Thr Cys Ile Pro Gly Val Ile Glu Tyr Lys Gly Ala Asn Ile Gln 100 105 110 Leu Leu Asp Leu Pro Gly Ile Ile Glu Gly Ala Ala Gln Gly Lys Gly 115 120 125 Arg Gly Arg Gln Val Ile Ala Val Ala Arg Thr Ala Asp Val Ile Ile 130 135 140 Met Met Leu Asp Ala Thr Lys Gly Glu Val Gln Arg Ser Leu Leu Glu 145 150 155 160 Lys Glu Leu Glu Ser Val Gly Ile Arg Leu Asn Lys His Lys Pro Asn 165 170 175 Ile Tyr Phe Lys Pro Lys Lys Gly Gly Gly Ile Ser Phe Asn Ser Thr 180 185 190 Val Thr Leu Thr Gln Cys Ser Glu Lys Leu Val Gln Leu Ile Leu His 195 200 205 Glu Tyr Lys Ile Phe Asn Ala Glu Val Leu Phe Arg Glu Asp Cys Ser 210 215 220 Pro Asp Glu Phe Ile Asp Val Ile Val Gly Asn Arg Val Tyr Met Pro 225 230 235 240 Cys Leu Tyr Val Tyr Asn Lys Ile Asp Gln Ile Ser Met Glu Glu Val 245 250 255 Asp Arg Leu Ala Arg Lys Pro Asn Ser Val Val Ile Ser Cys Gly Met 260 265 270 Lys Leu Asn Leu Asp Tyr Leu Leu Glu Met Leu Trp Glu Tyr Leu Ala 275 280 285 Leu Thr Cys Ile Tyr Thr Lys Lys Arg Gly Gln Arg Pro Asp Phe Thr 290 295 300 Asp Ala Ile Ile Leu Arg Lys Gly Ala Ser Val Glu His Val Cys His 305 310 315 320 Arg Ile His Arg Ser Leu Ala Ser Gln Phe Lys Tyr Ala Leu Val Trp 325 330 335 Gly Thr Ser Thr Lys Tyr Ser Pro Gln Arg Val Gly Leu Thr His Thr 340 345 350 Met Glu His Glu Asp Val Ile Gln Ile Val Lys Lys 355 360 <210> 2 <211> 1095 <212> DNA <213> Homo sapiens <400> 2 atggggatct tagagaagat ctcggagatc gagaaggaga tcgctcggac acagaagaac 60 aaggccactg agtatcatct gggcctgctg aaagctaagc tcgccaagta tcgggcccag 120 ctcctggaac cgtccaaatc ggcctcgtcc aaaggagagg gctttgatgt catgaagtcg 180 ggtgatgccc gtgtggcgct gattggattt ccctctgtgg gtaagtccac attcttgagt 240 ctgatgacct ccacggccag cgaggcagcg tcctatgagt tcaccactct gacgtgtatt 300 cctggggtca ttgaatacaa aggtgccaac atccagctcc tggaccttcc tggaatcatt 360 gaaggcgcag cccaaggaaa aggccgtggc cggcaggtga tcgctgtggc gcgcacggct 420 gacgtcatca tcatgatgct ggatgccacc aagggagagg tgcagaggtc tctgctggag 480 aaggagctgg agtctgtggg catccgcctc aacaagcaca agcctaacat ctacttcaag 540 cccaagaaag gtggtggcat ctcctttaac tcgacagtca cgctgaccca gtgctcggaa 600 aagctggtgc agctcatcct gcacgaatac aagatcttca atgcagaagt gcttttccga 660 gaagactgct ccccggacga gttcatcgat gtgatcgtgg gcaaccgggt gtacatgccc 720 tgcctgtatg tttataacaa aatcgaccag atctccatgg aagaggtgga ccgcctggcc 780 cgaaaaccca acagtgtggt catcagctgc ggcatgaagc tgaacctgga ctatctgctg 840 gagatgcttt gggaggtactt ggccctgacc tgcatctaca ccaagaagag aggacagagg 900 ccagacttca cagacgccat cattctccgg aaaggggcct cagtggagca cgtgtgccac 960 cgcatccacc ggtcactcgc cagccagttc aagtacgccc tggtgtgggg caccagcacc 1020 aagtacagtc cgcagcgggt gggcctgacc cacaccatgg agcatgagga cgtcatccag 1080 atcgtgaaga agtaa 1095

Claims (9)

A pharmaceutical composition for preventing or treating sepsis, comprising a developmentally-regulated GTP-binding protein 2 (DRG2) inducer as an active ingredient. According to claim 1,
The inducer is a pharmaceutical composition for preventing or treating sepsis, characterized in that the DRG2 gene expression promoter or activator of the DRG2 protein. According to claim 1,
The inducer is DRG2 protein; Or a pharmaceutical composition for preventing or treating sepsis, characterized in that the expression vector contains a polynucleotide encoding the DRG2 protein. According to claim 3,
The DRG2 protein is a pharmaceutical composition for preventing or treating sepsis, characterized in that it comprises the amino acid sequence represented by SEQ ID NO: 1. According to claim 3,
The polynucleotide is a pharmaceutical composition for preventing or treating sepsis, characterized in that it comprises the nucleotide sequence represented by SEQ ID NO: 2. According to claim 1,
The sepsis is a pharmaceutical composition for preventing or treating sepsis, characterized in that sepsis or septic shock. a) treating DRG2 (Developmentally-regulated GTP-binding protein 2) gene or cells containing DRG2 protein with a candidate substance;
b) measuring the expression level of the DRG2 gene or the activity of the DRG2 protein; and
c) a method for selecting a substance for preventing or treating sepsis, comprising the step of classifying a substance for preventing or treating sepsis when the expression level of the DRG2 gene or the activity of the DRG2 protein is increased. According to claim 7,
The step of measuring the expression level of the DRG2 gene or the activity of the DRG2 protein is reverse transcriptase-polymerase chain reaction, real time-polymerase chain reaction, western blotting, northern blotting Any one selected from the group consisting of rutting, ELISA (enzyme linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, immunoprecipitation assay, and immunohistochemical analysis A method for selecting a substance for preventing or treating sepsis, characterized by measuring by the above method. According to claim 7,
The candidate material is any one selected from the group consisting of nucleic acids, peptides, aptamers, proteins, compounds, natural products, natural extracts and lipids, a method for screening substances for preventing or treating sepsis.

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