Podocyte impairment is a key pathogenic even in the initiation and development of glomerular diseases associated with proteinuria. The type 2 diabetic patients is characterized by progressive increases in albuminuria which are associated with the development of characteristic histopathological features. Losartan had a benefit in decreasing albuminuria in type 2 diabetic patients,suggesting that losartan may have another effect other than blockade of the traditional renin-angiotensin system (RAS). However, the mechanism has remained undetermined. Glucose transporter 1 (GLUT1) is the predominant basal glucose transporter. In the kidney, GLUT1 was overexpressed predominantly in glomerular mesangial cells and in small vessels, rather than in podocytes. The increased glomerular GLUT1 mimicked diabetes-induced glomerular GLUT1 expression. In this study, we hypothesized that increased GLUT1 expression induced by angiotensinII (AngII) contributes to the progression of podocytes injury, losartan can block the effect of AngII and protect podocytes via stabilizing the expression of GLUT1, our results strongly suggest that losartan has a direct and protective effect on podocytes. This represents a novel mechanism by which losartan may protect podocyte from apoptotic death and improve podocyte function via stabilizing the expression of GLUT1. This finding underlines the crucial role of GLUT1 in the pathogenesis of podocyte injury and proteinuria.
Objective:
the objective of this article is to evaluate the role of siRNA-silenced TRPC6 on podocyte autophagy and apoptosis induced by AngII.
Methods:
mouse podocyte cell lines were cultured in vitro. The apoptosis rates of each group were detected using flow cytometry. The expression of LC3-II protein and changes in distribution were detected by confocal laser, and the western blot protocol was employed for detection of protein expression of LC3-II.
Results:
AngII-injured podocyte had a significant increase in apoptosis, while silencing TRPC6 could decrease the apoptosis induced by AngII. Autophagy remarkably increased after AngII injury. While silencing TRPC6 stabilized the autophagy expression, AngII could activate the autophagy of podocyte. Autophagy-associated protein LC3-II expression increased after AngII injury. The LC3-II mRNA and the protein level could be down regulated by 3-MA. The silencing of TRPC6 could stabilize the autophagy expression.
Conclusion:
the data suggest that AngII can lead to podocyte injury. Autophagy may have beneficial effects in preventing the progression of proteinuria. This study provides some new clues for further exploring the occurrence of podocyte injury and the development mechanism of proteinuria.
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