Role of cell signaling pathway in mesangial cells in the progression of chronic kidney disease

• Project/Area Number: 24591202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: NAGAI Kojiro 徳島大学, 大学病院, 講師 (40542048)
• Co-Investigator(Kenkyū-buntansha): MATSUURA Motokazu 徳島大学, 病院, 助教 (10403734) ; TOMINAGA Tatsuya 徳島大学, ヘルスバイオサイエンス研究部, 助教 (80425446)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 慢性腎臓病 / 細胞伝達経路 / メサンギウム細胞 / 糸球体硬化 / mTOR経路 / smad1

Outline of Final Research Achievements

Mesangial cells have been suggested to be related to the progression of chronic kidney disease in vitro. Therefore, an analysis of the role of mesangial cells by using a new site-specific gene knockout system was performed. Foxd1-Cre or tammoxifen induced Foxd1-Cre mice were mated with TSC1 floxed mice. Knockout of TSC1 caused mammalian target of rapamycin(mTOR) pathway activation in mesangial cells. Then, extracellular matrix in mesangial cells increased. It is the first finding which proves that mesangial-specific cell signal pathway activation can induce chronic kidney disease in vivo.