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Comment
. 2015;11(12):2385-6.
doi: 10.1080/15548627.2015.1115173.

Emerging role of podocyte autophagy in the progression of diabetic nephropathy

Mako Yasuda-Yamahara  1 , Shinji Kume  1 , Atsuko Tagawa  1 , Hiroshi Maegawa  1 , Takashi Uzu  1
Affiliations
Comment

Emerging role of podocyte autophagy in the progression of diabetic nephropathy

Mako Yasuda-Yamahara et al. Autophagy. 2015.

Abstract

Glomerular podocytes are pivotal in maintaining glomerular filtration barrier function. As severe podocyte injury results in proteinuria in patients with diabetic nephropathy, determining the pathogenesis of podocyte injury may contribute to the development of new treatments. We recently showed that autophagy is involved in the pathogenesis of diabetes-related podocyte injury. Insufficient podocyte autophagy and podocyte loss are observed in diabetic patients with massive proteinuria. Podocyte loss and massive proteinuria occur in high-fat diet-induced diabetic mice with podocyte-specific autophagy deficiency, with podocytes of these mice and of diabetic rats having huge damaged lysosomes. Sera from diabetic patients and from rodents with massive proteinuria cause autophagy insufficiency, resulting in lysosome dysfunction and apoptosis of cultured podocytes. These findings suggest the importance of autophagy in maintaining lysosome homeostasis in podocytes under diabetic conditions. Impaired autophagy may be involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy.

Keywords: MTORC1; autophagy; diabetic nephropathy; lysosome; podocyte injury; proteinuria.

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Figures

Figure 1.
Figure 1.
Autophagy insufficiency is associated with the pathogenesis of podocyte injury and massive proteinuria in diabetic nephropathy. Diabetes alone results in the development of mild glomerular lesions, such as glomerular hypertrophy, basement membrane (GBM) thickening, mild mesangial expansion and minimal proteinuria, leading to slowly-progressive renal dysfunction. However, the combination of insufficient podocyte autophagy and diabetic conditions results in podocyte loss, foot process alterations and lysosome dysfunction. This results in massive refractory proteinuria and a rapid decline of renal function. Autophagy insufficiency-related podocyte loss may be involved in the "point of no return" in diabetic nephropathy.
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