Analysis for PMEPA1 expression in the pathogenesis of dermal fibrosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17807
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Yokohama City University
• Principal Investigator: WATANABE Tomoya 横浜市立大学, 医学部, 助教 (00733461)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 皮膚線維化 / 全身性強皮症 / 創傷治癒

Outline of Final Research Achievements

We analyzed the expression of PMEPA1 mRNA and protein in human skin fibroblasts and skin samples. The expression of PMEPA1 was significantly increased time-dependently by TGF-β stimulation. However, there was no difference in mRNA expression between skin fibroblasts derived from patients with systemic sclerosis(SSc) and normal skin fibroblasts. The immunohistochemistry showed similar results. In addition, knockdown of PMEPA1 using siRNA in SSc skin fibroblasts showed no significant changes in the expression of skin fibrosis-related genes. On the other hand, analysis using a mouse model of wound healing showed increased the expression levels of PMEPA1 in skin ulcer. These results suggested that PMEPA1 is involved in the pathogenesis of skin fibrosis during the wound healing process.

Free Research Field

皮膚線維化

Academic Significance and Societal Importance of the Research Achievements

本研究は皮膚線維化におけるPMEPA1の病態関与について解析し、PMEPA1が創傷治癒過程における線維化に関連していることを示した。一方で、全身性強皮症のような線維化が完成された病態においては、PEMPA1の発現に変化がないことから、PMEPA1は創傷治癒などの初期の線維化病態に関与している可能性が示唆された。このTGF-βによって誘導されるPMEPA1の更なる機序を解析することで、皮膚における病的線維化の病態解明と治療に繋がると考えられた。