Molecular mechanisms of mesangial matrix expansion in the progression of diabetic nephropathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Matsubara Takeshi 京都大学, 医学(系)研究科(研究院), 講師 (90422964)
• Co-Investigator(Renkei-kenkyūsha): YANAGITA Motoko 京都大学, 大学院医学研究科・腎臓内科学, 教授 (70378769)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 病理学 / 糖尿病性腎症

Outline of Final Research Achievements

Diabetic nephropathy is pathologically characterized by the accumulation of extracellular matrix in the mesangium, of which the main component is α1/α2 type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic conditions in vitro. Here, we demonstrate that Smad1 plays a key role in diabetic nephropathy through bone morphogenetic protein 4 (BMP4) in vivo. Smad1-overexpressing mice were established, and the induction of diabetes resulted in greater mesangial expansion. We also identified BMP4 as a regulatory factor of Smad1 in diabetic nephropathy and showed that diabetic mice treated with a BMP4-neutralizing antibody exhibited decreased Smad1 phosphorylation and less mesangial expansion than those with control IgG. Our data indicate that BMP4/Smad1 signaling is a critical cascade for the progression of mesangial expansion and that blocking this signal could be a novel therapeutic strategy for diabetic nephropathy.

Free Research Field

腎臓内科学