Abstract
It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN). Here we used shRNA transfection to knockdown the insulin receptor (IR) gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation. The present study deepens our understanding of the role of autophagy in the pathogenesis of DN.
Highlights
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease (ESRD) worldwide
Our results show that autophagy related proteins such as Beclin1 and LC3 were down regulated and p62 was increased in insulin receptor (IR)-knockdown podocytes
Our data indicates decreased autophagy activity is induced in podocytes under insulin resistant conditions
Summary
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease (ESRD) worldwide. It is a major devastating complication of diabetes mellitus (DM), with up to 40% of diabetic patients experiencing this problem (Shi & Hu, 2014). The natural history of DN is dominated by progressive albuminuria, and podocytes are key components of the ultrafiltration system in the glomeruli. Podocyte number and morphology have been proved to be predictors of DN progression. This makes the glomerular podocyte an attractive early target cell. Molecular mechanisms involved in the etiology and progression of DM and its complications have been studied intensively.
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