2013 Fiscal Year Final Research Report

Role of autophagy in the pathogenesis of diabetic nephropathy

Research Project

Project/Area Number	24890089
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Kidney internal medicine
Research Institution	Shiga University of Medical Science
Principal Investigator	MORITA Yoshikata 滋賀医科大学, 医学部, 特任助教 (40636130)
Project Period (FY)	2012-08-31 – 2014-03-31
Keywords	糖尿病性腎症
Research Abstract	Diabetic nephropathy is a leading cause of end stage of renal disease. Thus new therapeutic strategy is urgently required. Hyperactivation of mTORC1 signal in podocytes has been reported to be strongly associated with the progression of diabetic nephropathy. However, the detailed mechanism underlying diabetes-related mTORC1 activation has remained unclear. In this study, we have revealed that saturated fatty acid is a potent activator of mTORC1 and subsequent inducer of apoptosis in podocytes. Furthermore, autophagy insufficiency related to mTORC1 hayperactivation was strongly associated with the progression of podocyte dysfunction and subsequent proteinuria in mice. The results suggest that inhibition of free fatty acid-mediated mTORC1 activation and activation of autophagy in podocytes are new therapeutic strategies for diabetic nephropathy.