Elucidation of the oxidation stress-dependent Wnt signaling on renal fibrosis
| Project/Area Number |
24591220
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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 |
Kidney internal medicine
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
SATOH Minoru 川崎医科大学, 医学部, 准教授 (70449891)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIHARA Naoki 川崎医科大学, 医学部, 教授 (10233701)
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| Research Collaborator |
KADOYA Hiroyuki 川崎医科大学, 医学部, 臨床助教
IHORIYA Chieko 川崎医科大学, 医学部, 臨床助教
YORIMASA Etsuko 川崎医科大学, 医学部, 研究補助員
HANADA Satomi 川崎医科大学, 医学部, 研究補助員
SATOH Keiko 川崎医科大学, 医学部, 研究補助員
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 線維化 / 細胞周期 / Wnt / FOXO / 酸化ストレス / G2/M / 腎臓 / 老化 |
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| Outline of Final Research Achievements |
We hypothesized that oxidative stress-dependent β-catenin signaling could promote renal fibrosis by leading to cell cycle arrest at the G2/M phase in tubular epithelial cells. In vitro experiment, we examined whether the profibrotic cytokine expression at the G2/M phase is increased by Wnt3a stimulation with oxidative stress in human proximal tubule epithelial cells. In vitro, cell cycle arrest in G2/M phase was increased by the Wnt stimulation under the presence of hydrogen peroxide. In addition, Wnt3a with hydrogen peroxide also increased growth arrest and DNA-damage-inducible protein 45a and cyclin G2 genes with increase of β-catenin/FOXO complex. In the G2/M phase cells, transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) expressions were increased. Oxidative stress with Wnt stimulation induces G2/M cell cycle arrest and increases profibrotic cytokine production. Reduction of the oxidative stress could ameliorate the renal fibrosis.
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Report
(4 results)
Research Products
(11 results)
