A novel role for Nox1/NADPH oxidase in cardiac fibrosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: IWATA KAZUMI 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60305571)
• Co-Investigator(Kenkyū-buntansha): 松本 みさき 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80533926)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 心線維化 / 活性酸素種 / 心線維芽細胞 / 心筋細胞 / ゲノム編集

Outline of Final Research Achievements

In this study, we demonstrated a novel role for NOX1, a non-phagocytic isoform of superoxide-producing NADPH oxidase, in cardiac fibrosis following drug-induced myocardial injury. A single-dose administration of doxorubicin (DOX) caused severe cardiac fibrosis in wild-type mice, but it was significantly attenuated in Nox1-deficient mice. When H9c2 cardiomyocytes were exposed to their homogenate, a dose-dependent increase in NOX1 mRNA was observed. When isolated cardiac fibroblasts were exposed to H9c2 homogenates, increased proliferation and up-regulation of collagen 3a1 mRNA were demonstrated. These changes were significantly attenuated in cardiac fibroblasts exposed to homogenates from H9c2 harboring disrupted Nox1. These findings suggest that up-regulation of NOX1 following cellular damage promotes cardiac fibrosis by aggravating the pro-fibrotic response of cardiac fibroblasts.

Free Research Field

病態分子薬理学