Elucidation of the oxidation stress-dependent Wnt signaling on renal fibrosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: SATOH Minoru 川崎医科大学, 医学部, 准教授 (70449891)
• Co-Investigator(Kenkyū-buntansha): KASHIHARA Naoki 川崎医科大学, 医学部, 教授 (10233701)
• 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
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 線維化 / 細胞周期 / Wnt / FOXO

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.

Free Research Field

腎臓