%0 Journal Article
%T The Role of Autophagy in the Pathogenesis of Diabetic Nephropathy
%A Kosuke Yamahara
%A Mako Yasuda
%A Shinji Kume
%A Daisuke Koya
%A Hiroshi Maegawa
%A Takashi Uzu
%J Journal of Diabetes Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/193757
%X Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The multipronged drug approach targeting blood pressure and serum levels of glucose, insulin, and lipids fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to combat diabetic nephropathy is required. Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells and plays a critical role in maintaining cellular homeostasis. The accumulation of proteins and organelles damaged by hyperglycemia and other diabetes-related metabolic changes is highly associated with the development of diabetic nephropathy. Recent studies have suggested that autophagy activity is altered in both podocytes and proximal tubular cells under diabetic conditions. Autophagy activity is regulated by both nutrient state and intracellular stresses. Under diabetic conditions, an altered nutritional state due to nutrient excess may interfere with the autophagic response stimulated by intracellular stresses, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing the relationships between autophagy and diabetic nephropathy and suggest the therapeutic potential of autophagy in diabetic nephropathy. 1. Introduction The increasing prevalence of diabetes mellitus and its vascular complications has become a major health problem worldwide. Diabetic nephropathy is a serious complication of diabetes and is a common cause of end-stage renal disease. Diabetes induces glomerular damage, along with proteinuria, and subsequent tubulointerstitial lesions, leading to end-stage renal disease [1¨C3]. Initially, the patient shows hyperfiltration, represented by high glomerular filtration rates (GFRs) and occasional occurrence of microalbuminuria. Later, the patient shows a gradual decline in the GFR and persistence of microalbuminuria that comes before mild and subsequently moderate proteinuria. Urinary protein seems to be almost entirely reabsorbed in early and late proximal tubules and may induce tubulointerstitial damage [3]. Reducing proteinuria by keeping blood pressure and blood glucose levels under control is therefore a primary therapeutic goal with diabetic nephropathy [4, 5]. Unfortunately, however, some patients develop treatment-resistant proteinuria, resulting in end-stage renal disease. There is now an urgent need to identify new therapeutic target molecules or cellular processes that underlie the pathogenesis of diabetic nephropathy to establish additional
%U http://www.hindawi.com/journals/jdr/2013/193757/