The mechanism of promoting abnormal scar formation with periostin in dermal fibroblasts

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16986
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Osaka University
• Principal Investigator: MAEDA DAISUKE 大阪大学, 医学系研究科, 助教 (60772465)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ケロイド / 肥厚性瘢痕 / ペリオスチン

Outline of Final Research Achievements

The mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-b1 (TGF-b1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-b1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-b1 secretion. Secreted TGF-b1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.

Free Research Field

形成外科

Academic Significance and Societal Importance of the Research Achievements

ペリオスチンは、創傷治癒過程において必要なタンパクである。しかし過剰なペリオスチンが異常瘢痕形成の一因であることが、本研究において示唆された。難治性と考えられているケロイド、肥厚性瘢痕の治療法の1つとしてペリオスチンに着目することで、通常の瘢痕すら残さない(scarless wound healing)医療の開発に発展すれば、 人類全体の QOL 向上に大きく貢献できると考えられる。