Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
23.05.2011
Gödel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S, Debreczeni-Mór A, Lindenmeyer MT, Rastaldi MP, Hartleben G, Wiech T, Fornoni A, Nelson RG, Kretzler M, Wanke R, Pavenstädt H, Kerjaschki D, Cohen CD, Hall MN, Rüegg MA, Inoki K, Walz G, Huber TB.
J Clin Invest. 2011;121(6):2197-209
Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 in mouse podocytes induced proteinuria and progressive glomerulosclerosis. In contrast, increased mTOR activity accompanied human diabetic nephropathy. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes significantly ameliorated the progression of of glomerular disease in diabetic nephropathy.
