The role of microRNA146b-5p for scar-less healing in skin wounds

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Toho University
• Principal Investigator: Akasaka Yoshikiyo 東邦大学, 医学部, 教授 (60202511)
• Co-Investigator(Kenkyū-buntansha): 藤澤 千恵 東邦大学, 医学部, 講師 (10393000) ; 大西 清 東邦大学, 医学部, 名誉教授 (30194228) ; 中道 美保 東邦大学, 医学部, 助教 (70804178)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 皮膚 / 瘢痕 / microRNA / 線維芽細胞 / bFGF / PDGFα / 脂肪組織 / 創傷治癒

Outline of Final Research Achievements

We found miRNA146b-5p preferentially upregulated in wound fibroblasts by bFGF and identified PDGFRα as a direct target of miRNA146b-5p. miRNA146b-5p led to markedly repressed fibrosis in skin wounds, with decreased expression of PDGFRα in wounds. These results indicate the positive effects of miRNA146b-5p for the suppression of fibrosis, possibly through the inhibition of PDGFRα. Notably, we discovered the specific colocalization of the exosome marker CD81 and miRNA146b-5p in the fibroblastic cells of adipose tissues following mimic transfection. Therefore, fibroblastic cells of adipose tissues, which may specifically pick up and contain miRNA146b-5p via exosome, may play an important role in the suppression of dermal fibrosis. In this process, miRNA146b-5p may inhibit PDGFRα expression in fibro-adipogenic progenitors, which will lead to the inhibition of wound fibrosis via the repression of PDGFRα-induced profibrotic activities along with myofibroblast transition.

Free Research Field

組織修復学

Academic Significance and Societal Importance of the Research Achievements

我々はラットの実験系を用いて皮膚傷痕の瘢痕を小さくするmicroRNA146b-5pを世界で初めて明らかにしました。皮膚の傷口は目立たない瘢痕になりますが、ケロイドや肥厚性瘢痕では逆に瘢痕が大きくなります。本研究ではmicroRNA146b-5pによりラット皮膚傷痕の瘢痕が小さくなる新知見を明らかにしました。本研究の成果は、microRNA146b-5pが皮膚の傷痕における瘢痕線維化の抑制メカニズムを解明するのみならず、microRNA146b-5pを直接投与することで傷害臓器で生じる線維化を抑制して線維化臓器における機能不全の予防につながることが期待されます。