Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis

Yue Zhang; Ying Wang; Lin Zeng; Yixiang Liu; Huiling Sun; Shanshan Li; Siyu Wang; Longjun Shu; Naixin Liu; Saige Yin; Junsong Wang; Dan Ni; Yutong Wu; Ying Yang; Li He; Buliang Meng; Xinwang Yang

doi:10.1093/burnst/tkac032

您当前的位置：

首页 >

文章列表页 >

Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis

更新时间：2023-09-05

- Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis
- Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis
- Burns & Trauma 2022年10卷第1期
- 作者机构：
  
  1. Department of Anatomy and Histology & Embryology
  2. Kunming Medical University
  3. Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes
  4. Yunnan MinZu University
  5. Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences
  6. Endocrinology Department of Affiliated Hospital of Yunnan University
  7. Department of Dermatology, First Affiliated Hospital of Kunming Medical University
- 作者简介：
- 基金信息：
  
  This work was supported by grants from the National Natural Science Foundation of China (81760648, 32060212 and 82160159), Yunnan Applied Basic Research Project Foundation (2019FB128), Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (202101AY070001-006 and 2019FE001(-183)), Program for Innovative Research Team in Ministry of Education of China (IRT17-R49), Science and Technology Leadership Talent Project in Yunnan China (2017HA010), Endocrine Clinical Medical Center of Yunnan Province (ZX2019-02-02) and the Innovative Team of Precise Prevention and Treatment against Metabolic Diseases of Yunnan University, Scientific Research Fund Projects from the Department of Education of Yunnan Province (2021 J0205).
- DOI：10.1093/burnst/tkac032
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-7-12，
扫描看全文
Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis[J]. Burns & Trauma, 2022,10(1).

Yue Zhang, Ying Wang, Lin Zeng, Yixiang Liu, Huiling Sun, Shanshan Li, Siyu Wang, Longjun Shu, Naixin Liu, Saige Yin, Junsong Wang, Dan Ni, Yutong Wu, Ying Yang, Li He, Buliang Meng, Xinwang Yang, Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis, Burns & Trauma, Volume 10, 2022, tkac032, https://doi.org/10.1093/burnst/tkac032
Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis[J]. Burns & Trauma, 2022,10(1). DOI： 10.1093/burnst/tkac032.

Yue Zhang, Ying Wang, Lin Zeng, Yixiang Liu, Huiling Sun, Shanshan Li, Siyu Wang, Longjun Shu, Naixin Liu, Saige Yin, Junsong Wang, Dan Ni, Yutong Wu, Ying Yang, Li He, Buliang Meng, Xinwang Yang, Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis, Burns & Trauma, Volume 10, 2022, tkac032, https://doi.org/10.1093/burnst/tkac032 DOI：

摘要

Abstract

BackgroundAmphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However

further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate

as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.MethodsA combination of Edman degradation

mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells)

hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS

scratch healing and a Transwell experiment against HaCaT cells

full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis

enzyme-linked immunosorbent assay

real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.ResultsA novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence ‘GLFKWHPRCGEEQSMWT’ was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity

but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically

OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1 (TGF-β1) and activate the subsequent TGF-β1/Smad signaling pathway

thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.ConclusionsOur results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.

关键词

Keywords

microRNAmiR-663aWound healingPeptideAmphibianHuman keratinocytesOA-G17dChronic woundskinTransforming growth factor-β1Smad

references

1.Zhao Y, Wang Q, Jin Y, Li Y, Nie C, Huang P, et al. Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1, Targeting FGFR2IIIc for Skin Wound Healing. Cell Physiol Biochem. 2018;49:1033–48.

2.Lee JH, Kim HL, Lee MH, You KE, Kwon BJ, Seo HJ, et al. Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model. Phytomedicine. 2012;19:1223–7.

3.Yang F, Bai X, Dai X, Li Y. The biological processes during wound healing. Regen Med. 2021;16:373–90.

4.Chen C, Meng Z, Ren H, Zhao N, Shang R, He W, et al. The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing. Burns Trauma. 2021;9:tkab009. https://doi.org/10.1093/burnst/tkab009.

5.Sansbury BE, Li X, Wong B, Riley CO, Shay AE, Nshimiyimana R, et al. PCTR1 Enhances Repair and Bacterial Clearance in Skin Wounds. Am J Pathol. 2021;191:1049–63.

6.Han G, Ceilley R. Chronic Wound Healing: A Review of Current Management and Treatments. Adv Ther. 2017;34:599–610.

7.Rinaldi AC. Antimicrobial peptides from amphibian skin: an expanding scenario. Curr Opin Chem Biol. 2002;6:799–804.

8.Barra D, Simmaco M. Amphibian skin: a promising resource for antimicrobial peptides. Trends Biotechnol. 1995;13:205–9.

9.Li X, Wang Y, Zou Z, Yang M, Wu C, Su Y, et al. OM-LV20, a novel peptide from odorous frog skin, accelerates wound healing in vitro and in vivo. Chem Biol Drug Des. 2018;91:126–36.

10.Liu N, Li Z, Meng B, Bian W, Li X, Wang S, et al. Accelerated Wound Healing Induced by a Novel Amphibian Peptide (OA-FF10). Protein and peptide letters. 2019;26:261–70.

11.Wang Y, Feng Z, Yang M, Zeng L, Qi B, Yin S, et al. Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds. Pharmacol Res. 2021;163:105296. https://doi.org/10.1016/j.phrs.2020.105296.

12.Bian W, Meng B, Li X, Wang S, Cao X, Liu N, et al. OA-GL21, a novel bioactive peptide from Odorrana andersonii, accelerated the healing of skin wounds. Biosci Rep. 2018;38:BSR20180215. https://doi.org/10.1042/BSR20180215.

13.Yin S, Yang M, Li Y, Li S, Fu Z, Liu N, et al. Peptide OM-LV20 exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats. Biochem Biophys Res Commun. 2021;537:36–42.

14.Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 2010;62:1733–43.

15.Hao B, Wang X, Ma X, Jin Y, Fan W, Laba C, et al. Preparation of complex microcapsules of soluble polysaccharide from Glycyrrhiza uralensis and its application in wound repair and scar inhibition. Int J Biol Macromol. 2020;156:906–17.

16.De Felice B, Manfellotto F, Garbi C, Santoriello M, Nacca M. miR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid fibroblasts. Mol Med Rep. 2018;17:7081–8.

17.Icli B, Wu W, Ozdemir D, Li H, Haemmig S, Liu X, et al. MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells. FASEB J. 2019;33:5599–614.

18.Gallant-Behm CL, Piper J, Dickinson BA, Dalby CM, Pestano LA, Jackson AL. A synthetic microRNA-92a inhibitor (MRG-110) accelerates angiogenesis and wound healing in diabetic and nondiabetic wounds. Wound Repair Regen. 2018;26:311–23.

19.Yang Z, Duan X, Wang X, Xu Q, Guo B, Xiang S, et al. The effect of Q-switched 1064-nm Nd: YAG laser on skin barrier and collagen synthesis via miR-663a to regulate TGFβ1/smad3/p38MAPK pathway. Photodermatol Photoimmunol Photomed. 2021;37:412–21.

20.Cao X, Wang Y, Wu C, Li X, Fu Z, Yang M, et al. Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing. Sci Rep. 2018;8:943. https://doi.org/10.1038/s41598-018-19486-9.

21.Cao X, Tang J, Fu Z, Feng Z, Wang S, Yang M, et al. Identification and Characterization of a Novel Gene-encoded Antioxidant Peptide from Odorous Frog Skin. Protein and peptide letters. 2019;26:160–9.

22.Shen Y, Maupetit J, Derreumaux P, Tufféry P. Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction. J Chem Theory Comput. 2014;10:4745–58.

23.Sun H, Wang Y, He T, He D, Hu Y, Fu Z, et al. Hollow polydopamine nanoparticles loading with peptide RL-QN15: a new pro-regenerative therapeutic agent for skin wounds. J Nanobiotechnology. 2021;19:304. https://doi.org/10.1186/s12951-021-01049-2.

24.Nirmal GR, Lin ZC, Tsai MJ, Yang SC, Alalaiwe A, Fang JY. Photothermal treatment by PLGA-gold nanorod-isatin nanocomplexes under near-infrared irradiation for alleviating psoriasiform hyperproliferation. J Control Release. 2021;333:487–99.

25.Meng YC, Mo XG, He TT, Wen XX, Nieh JC, Yang XW, et al. New bioactive peptides from the venom gland of a social hornet Vespa velutina. Toxicon. 2021;199:94–100.

26.Wei ZD, Sun YZ, Tu CX, Qi RQ, Huo W, Chen HD, et al. DNAJA4 deficiency augments hyperthermia-induced Clusterin and ERK activation: two critical protective factors of human keratinocytes from hyperthermia-induced injury. J Eur Acad Dermatol Venereol. 2020;34:2308–17.

27.Jang SI, Mok JY, Jeon IH, Park KH, Nguyen TT, Park JS, et al. Effect of electrospun non-woven mats of dibutyryl chitin/poly(lactic acid) blends on wound healing in hairless mice. Molecules. 2012;17:2992–3007.

28.Gp R, Mr R. Strontium ion cross-linked alginate-g-poly (PEGMA) xerogels for wound healing applications: in vitro studies. Carbohydr Polym. 2021;251:117119. https://doi.org/10.1016/j.carbpol.2020.117119.

29.Liu SJ, Meng MY, Han S, Gao H, Zhao YY, Yang Y, et al. Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorate HaCaT Cell Photo-Aging. Rejuvenation Res. 2021;24:283–93.

30.Xu Y, Lin Z, He L, Qu Y, Ouyang L, Han Y, et al. Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1. Oxid Med Cell Longev. 2021;9674809. https://doi.org/10.1155/2021/9674809.

31.Qin P, Meng Y, Yang Y, Gou X, Liu N, Yin S, et al. Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy. J Nanobiotechnology. 2021;19:309. https://doi.org/10.1186/s12951-021-01051-8.

32.Liu L, Yuan L, Huang D, Han Q, Cai J, Wang S, et al. miR-126 regulates the progression of epithelial ovarian cancer in vitro and in vivo by targeting VEGF-A. Int J Oncol. 2020;57:825–34.

33.Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020;19:43. https://doi.org/10.1186/s12943-020-01168-8.

34.Su JL, Ma K, Zhang CP, Fu X. Effect of human decidua mesenchymal stem cells-derived exosomes on the function of high glucose-induced senescent human dermal fibroblasts and its possible mechanism. Chin J Burns. 2022;38:170–83.

35.Zhou QY, Yang HM, Liu JX, Xu N, Li J, Shen LP, et al. MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7. Parasit Vectors. 2021;14:472. https://doi.org/10.1186/s13071-021-04972-3.

36.Wang J, Zhang Y, Song H, Yin H, Jiang T, Xu Y, et al. The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway. Mol Cancer. 2021;20:81. https://doi.org/10.1186/s12943-021-01375-x.

37.Jiang L, Ayre WN, Melling GE, Song B, Wei X, Sloan AJ, et al. Liposomes loaded with transforming growth factor β1 promote odontogenic differentiation of dental pulp stem cells. J Dent. 2020;103:103501. https://doi.org/10.1016/j.jdent.2020.103501.

38.Liu WN, Wu KX, Wang XT, Lin LR, Tong ML, Liu LL. LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM1 in neurosyphilis. Epigenomics. 2021;13:1187–203.

39.Yang J, Zhou Y, Ng SK, Huang KC, Ni X, Choi PW, et al. Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube. BMC Cancer. 2017;17:422. https://doi.org/10.1186/s12885-017-3417-z.

40.Li D, Sun Y, Wan Y, Wu X, Yang W. LncRNA NEAT1 promotes proliferation of chondrocytes via down-regulation of miR-16-5p in osteoarthritis. J Gene Med. 2020;22(9):e3203. https://doi.org/10.1002/jgm.3203.

41.Liu N, Meng B, Zeng L, Yin S, Hu Y, Li S, et al. Discovery of a novel rice-derived peptide with significant anti-gout potency. Food Funct. 2020;11:10542–53.

42.Yang X, Lee WH, Zhang Y. Extremely abundant antimicrobial peptides existed in the skins of nine kinds of Chinese odorous frogs. J Proteome Res. 2012;11:306–19.

43.Rezaii M, Oryan S, Javeri A. Curcumin nanoparticles incorporated collagen-chitosan scaffold promotes cutaneous wound healing through regulation of TGF-β1/Smad7 gene expression. Mater Sci Eng C Mater Biol Appl. 2019;98:347–57.

44.Guo J, Lin Q, Shao Y, Rong L, Zhang D. miR-29b promotes skin wound healing and reduces excessive scar formation by inhibition of the TGF-β1/Smad/CTGF signaling pathway. Can J Physiol Pharmacol. 2017;95:437–42.

45.André S, Raja Z, Humblot V, Piesse C, Foulon T, Sereno D, et al. Functional Characterization of Temporin-SHe, a New Broad-Spectrum Antibacterial and Leishmanicidal Temporin-SH Paralog from the Sahara Frog (Pelophylax saharicus). Int J Mol Sci. 2020;21(18):6713. https://doi.org/10.3390/ijms21186713.

46.Xie C, Fan Y, Yin S, Li Y, Liu N, Liu Y, et al. Novel amphibian-derived antioxidant peptide protects skin against ultraviolet irradiation damage. J Photochem Photobiol B. 2021;224:112327. https://doi.org/10.1016/j.jphotobiol.2021.

47.Zhang X, Feng C, Wang S, Wang Y, Fu Z, Zhang Y, et al. A novel amphibian-derived peptide alleviated ultraviolet B-induced photodamage in mice. Biomed Pharmacother. 2021;136:111258. https://doi.org/10.1016/j.biopha.2021.111258.

48.Liu N, Meng B, Bian W, Yang M, Shu L, Liu Y, et al. The beneficial roles of poisonous skin secretions in survival strategies of the odorous frog Odorrana andersonii. Naturwissenschaften. 2021;109(1):4. https://doi.org/10.1007/s00114-021-01776-4.

49.Ito D, Ito H, Ideta T, Kanbe A, Ninomiya S, Shimizu M. Systemic and topical administration of spermidine accelerates skin wound healing. Cell Commun Signal. 2021;19(1):36. https://doi.org/10.1186/s12964-021-00717-y.

50.Lai Y, Li D, Li C, Muehleisen B, Radek KA, Park HJ, et al. The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury. Immunity. 2012;37:74–84.

51.Ren H, Zhao F, Zhang Q, Huang X, Wang Z. Autophagy and skin wound healing. Burns Trauma. 2022;10:tkac003. https://doi.org/10.1093/burnst/tkac003.

52.Yan LJ, Fan XW, Yang HT, Wu JT, Wang SL, Qiu CG. MiR-93 inhibition ameliorates OGD/R induced cardiomyocyte apoptosis by targeting Nrf2. Eur Rev Med Pharmacol Sci. 2017;21:5456–61.

53.He QW, Li Q, Jin HJ, Zhi F, Suraj B, Zhu YY, et al. MiR-150 Regulates Poststroke Cerebral Angiogenesis via Vascular Endothelial Growth Factor in Rats. CNS Neurosci Ther. 2016;22:507–17.

54.Yang Q, Zhang Q, Qing Y, Zhou L, Mi Q, Zhou J. miR-155 is dispensable in monosodium urate-induced gouty inflammation in mice. Arthritis Res Ther. 2018;20(1):144. https://doi.org/10.1186/s13075-018-1550-y.

55.Schneider MR. MicroRNAs as novel players in skin development, homeostasis and disease. Br J Dermatol. 2012;166:22–8.

56.Liao YY, Zhang PH. Research advances on the role of competing endogenous RNAs in wound healing. Chin J Burns. 2022;38:84–9.

57.Reynolds LE, Conti FJ, Lucas M, Grose R, Robinson S, Stone M, et al. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med. 2005;11:167–74.

58.Yang Q, Ren GL, Wei B, Jin J, Huang XR, Shao W, et al. Conditional knockout of TGF-βRII /Smad2 signals protects against acute renal injury by alleviating cell necroptosis, apoptosis and inflammation. Theranostics. 2019;9:8277–93.

59.Sureshbabu A, Syed MA, Boddupalli CS, Dhodapkar MV, Homer RJ, Minoo P, et al. Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung. Respir Res. 2015;16:4. https://doi.org/10.1186/s12931-014-0162-6.

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Autophagy and skin wound healing

Metabolic reprogramming in skin wound healing

Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis

PC4 serves as a negative regulator of skin wound healing in mice

Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model