A study on signaling pathways associated with NOX4/NADPH oxidase for the development of new antifibrotic drugs
| Project/Area Number |
25460339
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto Prefectural University of Medicine |
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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)
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| 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)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 活性酸素 / NADPHオキシダーゼ / 線維化 |
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| 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.
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Report
(4 results)
Research Products
(3 results)
