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KMID : 1200020150390060451
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Diabetes & Metabolism Journal
2015 Volume.39 No. 6 p.451 ~ p.460
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Autophagy: A Novel Therapeutic Target for Diabetic Nephropathy
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:Shinji Kume
:Daisuke Koya
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Abstract
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Diabetic nephropathy is a leading cause of end stage renal disease and its occurance is increasing worldwide. The most effective treatment strategy for the condition is intensive treatment to strictly control glycemia and blood pressure using renin-angiotensin system inhibitors. However, a fraction of patients still go on to reach end stage renal disease even under such intensive care. New therapeutic targets for diabetic nephropathy are, therefore, urgently needed. Autophagy is a major catabolic pathway by which mammalian cells degrade macromolecules and organelles to maintain intracellular homeostasis. The accumulation of damaged proteins and organelles is associated with the pathogenesis of diabetic nephropathy. Autophagy in the kidney is activated under some stress conditions, such as oxidative stress and hypoxia in proximal tubular cells, and occurs even under normal conditions in podocytes. These and other accumulating findings have led to a hypothesis that autophagy is involved in the pathogenesis of diabetic nephropathy. Here, we review recent findings underpinning this hypothesis and discuss the advantages of targeting autophagy for the treatment of diabetic nephropathy.
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KEYWORD
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AMP-activated protein kinases, Autophagy, Caloric restriction, Diabetic nephropathy, Mechanistic target of rapamycin complex 1, Podocytes, Sirt1, Tubular cell
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