Functional analysis of arginine methyltransferase 5 in cardiac fibrosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: University of Shizuoka
• Principal Investigator: KATANASAKA Yasufumi 静岡県立大学, 薬学部, 講師 (00583973)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アルギニンメチル化酵素 / 心不全 / 線維化

Outline of Final Research Achievements

Epigenetic regulatory mechanisms contribute to cardiac fibrosis, which is also a significant risk factor in the development and progression of heart failure. However, drug target molecules for fibrosis therapy have not been identified. In this study, we found that an arginine methyltransferase PRMT5 may be a molecule that promotes the differentiation of fibroblasts into myofibroblasts. EPZ015666, a selective inhibitor of PRMT5, was orally administered to mice and histological analysis and qRT-PCR were performed. Results showed that pressure overload-induced cardiac fibrosis and expression of fibrosis-related genes were significantly reduced by EPZ015666 treatment. Furthermore, in primary cultured cardiac fibroblasts, EPZ015666 suppressed histone methylation by PRMT5.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

PRMT5を介したアルギニンメチル化反応が心臓線維化において重要であることが考えられる。PRMT5は慢性心不全時における新規線維化治療標的になりうると考える。本研究成果はいまだ難治である心不全の治療薬開発、ひいては国民の健康維持に貢献する。