CN115404199A - Application of activin B in promoting hyaluronic acid synthesis - Google Patents
Application of activin B in promoting hyaluronic acid synthesis Download PDFInfo
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- CN115404199A CN115404199A CN202211353130.4A CN202211353130A CN115404199A CN 115404199 A CN115404199 A CN 115404199A CN 202211353130 A CN202211353130 A CN 202211353130A CN 115404199 A CN115404199 A CN 115404199A
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0656—Adult fibroblasts
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
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Abstract
The invention discloses application of activin B in promoting synthesis of hyaluronic acid. The activin B can promote fibroblasts to synthesize hyaluronic acid, and the quantity of the activin B promoting the fibroblasts to synthesize hyaluronic acid is obviously higher than that of the activin A. Therefore, the activin B can be applied to the preparation of medicaments or cosmetics with the effect of promoting the synthesis of the hyaluronic acid and has wide application prospect.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of activin B in promoting synthesis of hyaluronic acid.
Background
Fibroblasts are the main cellular component of loose connective tissue, differentiated from mesenchymal cells at the embryonic stage. In connective tissue, the primary function of fibroblasts is to synthesize various fibers and matrix components. Fibroblasts also exist in their functionally quiescent state, in the form of fibroblasts, which can transform into each other under certain conditions. Different types of connective tissue contain different numbers of fibroblasts.
The skin is composed of epidermis, dermis and hypodermis tissues and accessory organs, wherein the dermis of the skin is a connective tissue and is composed of a large number of fibers, extracellular matrix and various cells, and wherein the normal dermis of the skin has a large number of fibroblasts, which play an important role in the normal metabolic process of the skin. Fibroblasts in the dermis of the skin under normal conditions, mainly synthesize collagen fibers and elastic fibers of the dermis of the skin, and the mesomatrix component of the dermis of the skin: proteoglycan, mucin, and the like. The dermal tissue structural components of the skin undergo different structural changes of components with aging and trauma of the skin, and fibroblasts play an important role therein, so that it is extremely important to regulate the biological behavior of fibroblasts under different conditions.
Activins are an important group of cytokines discovered in recent years, and have been a focus of research because of their wide range of physiological actions. Sequence analysis shows that there are 4 kinds of human activin genes: INH β A, INH β B, INH β C and INH β E, where the number of exons in the gene is different in 4. First in humans INH β a is the most complex, containing 7 exons, and INH β B gene contains only two exons; secondly, 7 exons of the human INH β A gene are considered to be alternatively spliced and give rise to 3 different Act A protein variants, designated X1, X2 and X3 [1] . The activin forms four molecular structures of activin A, activin B, activin C and activin E respectively according to different combination forms of subunits beta A, beta B, beta C and beta E, and the researches on the activin C and the activin E are very few.
At present, by using a gene knockout mouse model, researches show that beta A-subunit and beta B-subunit have independent and independent functions in physiology, and the evaluation of ligand-receptor interaction shows that the receptor affinity between isoforms of activin subtypes is remarkably different [2] . It was found that activin- β a deficient mice developed to term, but died within 24 hours of birth. It has no beard and lower incisors and is deficient in secondary palatine areas including cleft palate, suggesting that activin- β a must play a role in craniofacial development [3] . Disruption of activin-beta B subunit gene resulting in eyelid development and female reproductive defects [4] . In thatThe locations of activin-beta A and beta B mRNA expression during skin wound healing were also different, activin-beta A mRNA being expressed mainly by mesenchymal cells of granulation tissue and activin-beta A mRNA being highly expressed mainly in proliferating keratinocytes [5] 。
The differences between the activin- β a-and β B subunits are not limited to differences in expression patterns, but are functionally different. It was found that when mice lacking the mature region of the β a subunit gene were complemented by the corresponding mature region of the activin- β B subunit gene, although some of the defects in β a subunit null mice were rescued and mice survived, they exhibited various defects, including hypogonadism, as well as reduction in body weight, life expectancy, female fertility and hair growth [6] . These defects are attributed to the non-overlapping function of the β a-and β B subunits. It was found that activin A promotes the expression of type I collagen in mouse and human fibroblasts [7] However, we found that activin B does not regulate collagen type I expression in mouse fibroblasts, and therefore different activins are thought to have non-overlapping functions. While the effect of activin B on fibroblasts is currently unknown.
[1] Billings PC, Bizzaro C, Yang E, Chung J, Mundy C, Pacifici M. Human and mouse activin genes: Divergent expression of activin A protein variants and identification of a novel heparan sulfate-binding domain in activin B. PLoS One. 2020 Feb 19;15(2):e0229254. doi: 10.1371/journal.pone.0229254. PMID: 32074129; PMCID: PMC7029874.
[2] Thompson TB, Cook RW, Chapman SC, Jardetzky TS, Woodruff TK. Beta A versus beta B: is it merely a matter of expression. Mol Cell Endocrinol. 2004 Oct 15;225(1-2):9-17. doi: 10.1016/j.mce.2004.02.007. PMID: 15451562.
[3] Matzuk MM, Kumar TR, Vassalli A, Bickenbach JR, Roop DR, Jaenisch R, Bradley A. Functional analysis of activins during mammalian development. Nature. 1995 Mar 23;374(6520):354-6. doi: 10.1038/374354a0. PMID: 7885473.
[4] Vassalli A, Matzuk MM, Gardner HA, Lee KF, Jaenisch R. Activin/inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Dev. 1994 Feb 15;8(4):414-27. doi: 10.1101/gad.8.4.414. PMID: 8125256.
[5] Beer HD, Gassmann MG, Munz B, Steiling H, Engelhardt F, Bleuel K, Werner S. Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair. J Investig Dermatol Symp Proc. 2000 Dec;5(1):34-9. doi: 10.1046/j.1087-0024.2000.00009.x. PMID: 11147673.
[6] Brown CW, Houston-Hawkins DE, Woodruff TK, Matzuk MM. Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nat Genet. 2000 Aug;25(4):453-7. doi: 10.1038/78161. PMID: 10932194.
[7] Wietecha MS, Pensalfini M, Cangkrama M, Müller B, Jin J, Brinckmann J, Mazza E, Werner S. Activin-mediated alterations of the fibroblast transcriptome and matrisome control the biomechanical properties of skin wounds. Nat Commun. 2020 May 25;11(1):2604. doi: 10.1038/s41467-020-16409-z. PMID: 32451392; PMCID: PMC7248062。
Disclosure of Invention
The invention discovers a cytokine-activin B capable of regulating fibroblasts to synthesize hyaluronic acid for the first time, wherein the activin B can promote the fibroblasts to synthesize hyaluronic acid and can be applied to preparing medicaments or cosmetics with the effect of promoting the synthesis of hyaluronic acid.
Accordingly, a first object of the present invention is to provide the use of activin B for promoting hyaluronic acid synthesis.
Preferably, the application of the activin B in promoting the synthesis of hyaluronic acid by fibroblasts is provided.
The second purpose of the invention is to provide the application of the activin B in preparing cosmetics and/or medicines for promoting the synthesis of hyaluronic acid.
It is a third object of the present invention to provide a cosmetic and/or pharmaceutical product for promoting hyaluronic acid synthesis, which contains activin B as an active ingredient.
Preferably, the cosmetics comprise water type cosmetics, emulsion type cosmetics and cream type cosmetics.
Preferably, the water-based cosmetic comprises a cosmetic water or a facial mask solution; the emulsion type cosmetics comprise skin lotion, skin care essence, eye essence, sleep mask, moisturizing gel or cleansing milk; the cream-type cosmetics comprise skin-care cream or eye cream.
Preferably, the medicine includes an internal medicine and an external medicine.
Preferably, the dosage forms of the internal medicine comprise powder, granules, capsules, tablets, pills, solutions, suspensions, emulsions, syrups and injections; the topical medicinal preparation is in the form of lotion, ointment, gel, tincture, liniment, spirit, powder, oil, cataplasm, plaster, plastics, and aerosol.
The invention firstly discovers a cytokine, namely activin B, capable of regulating fibroblasts to synthesize hyaluronic acid, wherein the activin B can promote the fibroblasts to synthesize hyaluronic acid, and the quantity of the activin B promoting the fibroblasts to synthesize hyaluronic acid is obviously higher than that of activin A, and P is less than 0.05. Therefore, the activin B can be applied to the preparation of medicaments or cosmetics with the effect of promoting the synthesis of the hyaluronic acid and has wide application prospect.
Drawings
FIG. 1 shows the results of the stimulation of hyaluronic acid synthesis by fibroblasts by activin B.
Detailed Description
The following examples are further illustrative of the present invention and are not intended to be limiting thereof.
Example 1
At a rate of 1X 10 per hole 5 Inoculating the individual skin fibroblast cells into 6-well plate, starving the cells with DMEM medium for 8 hr, adding cell mitosis inhibitor 10 pM Paclitaxel (Paclitaxel) to treat the cells for 72 hr, dividing the cells into control group, activin A group and activin B group, adding PBS to the control group, and adding activin A groupThe treatment was carried out by adding activin A to a final concentration of 10 ng/mL, and activin B to a final concentration of 10 ng/mL in the activin B group, and after 24 hours and 48 hours of culture, the content of hyaluronic acid in the cell supernatant was measured by Elisa, and each group was repeated 3 times. The results are shown in FIG. 1.
As can be seen from fig. 1, although activin a also promotes hyaluronic acid synthesis by fibroblasts, the amount of hyaluronic acid synthesis by activin B is significantly higher than that by activin a, P < 0.05.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.
Claims (6)
1. Use of activin B for promoting hyaluronic acid synthesis.
2. The use according to claim 1, for promoting hyaluronic acid synthesis by fibroblasts.
3. The application of activin B in preparing cosmetics and/or medicines for promoting hyaluronic acid synthesis.
4. A cosmetic for promoting hyaluronic acid synthesis, characterized by containing activin B as an active ingredient.
5. The cosmetic according to claim 4, wherein the cosmetic comprises a water-based cosmetic, an emulsion-based cosmetic or a cream-based cosmetic.
6. The cosmetic according to claim 5, wherein the aqueous cosmetic comprises a lotion or a mask solution; the emulsion type cosmetics comprise skin lotion, skin care essence, eye essence, sleep mask, moisturizing gel or cleansing milk; the cream-type cosmetic includes a skin cream or an eye cream.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115537393A (en) * | 2022-12-05 | 2022-12-30 | 广州优特佳生物科技发展有限公司 | Preparation method and application of umbilical cord mesenchymal stem cell directional secretion group for promoting hair growth |
Citations (6)
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|---|---|---|---|---|
| US20040052795A1 (en) * | 1995-10-21 | 2004-03-18 | Renovo Limited | Pharmaceutical composition containing an activin or inhibin stimulator |
| US20090117211A1 (en) * | 2007-11-01 | 2009-05-07 | Schneider Louise M | Compositions and methods for stimulating synthesis of pro-collagen or collagen and hyaluronic acid |
| JP2011042627A (en) * | 2009-08-21 | 2011-03-03 | Unitika Ltd | Hyaluronic acid synthesis promoter |
| CN103083721A (en) * | 2013-01-18 | 2013-05-08 | 南方医科大学 | Artificial skin graft for genipin immobilized activin B and preparation method thereof |
| TW201941776A (en) * | 2018-03-27 | 2019-11-01 | 日商生化學工業股份有限公司 | Agent for promoting hyaluronic acid synthesis, method for promoting hyaluronic acid synthesis, and method of evaluating cells |
| CN114258297A (en) * | 2019-08-21 | 2022-03-29 | 株式会社资生堂 | Cosmetic preparation |
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| CN115537393A (en) * | 2022-12-05 | 2022-12-30 | 广州优特佳生物科技发展有限公司 | Preparation method and application of umbilical cord mesenchymal stem cell directional secretion group for promoting hair growth |
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| CN115404199B (en) | 2023-03-21 |
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