A study on signaling pathways associated with NOX4/NADPH oxidase for the development of new antifibrotic drugs

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460339
• 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: Katsuyama Masato 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60315934)
• Co-Investigator(Renkei-kenkyūsha): ARAKAWA Noriaki 横浜市立大学, 生命ナノシステム科学研究科, 助教 (60398394) ; YABE Chihiro (NISHIMURA Chihiro) 京都府立医科大学, 大学院医学研究科, 教授 (70150571)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 活性酸素 / NADPHオキシダーゼ / 線維化

Outline of Final Research Achievements

It is well known that NOX4/NADPH oxidase is involved in fibrogenesis. Signaling pathways upstream and downstream of NOX4 were analyzed. A Smad binding element at approx. 75-base upstream of the transcription start site of the NOX4 gene was found essential for TGF-β-induced NOX4 expression. Proteomics analyses using cleavable isotope-coded affinity tags were carried out on a human lung fibroblast cell line stimulated with TGF-β to identify proteins that oxidized thiols were decreased by knock-down of NOX4. Among them, Protein X, an enzyme that has been thought to be involved in polymerization of extracellular matrices, was found decreased by knock-down of NOX4 at mRNA levels. On the other hand, Protein Z, of which function is unknown, was suggested to be a target of NOX4-derived reactive oxygen species (ROS). In a human neuroblastoma cells in which NOX4 is involved in cell proliferation, Protein A, a growth factor receptor, was suggested to be a target of NOX4-derived ROS.

Free Research Field

薬理学