The role of autophagy in the pathogenesis of diabetic nephropathy.
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.
Department of Medicine, Shiga University of Medical Science, Tsukinowa-Cho, Seta, Otsu, Shiga 520-2192, Japan.
Kosuke
K
Yamahara
Department of Medicine, Shiga University of Medical Science, Tsukinowa-Cho, Seta, Otsu, Shiga 520-2192, Japan.
Mako
M
Yasuda
Department of Medicine, Shiga University of Medical Science, Tsukinowa-Cho, Seta, Otsu, Shiga 520-2192, Japan.
Shinji
S
Kume
Diabetes & Endocrinology, Kanazawa Medical University, Daigaku 1-1, Kahoku-Gun, Uchinada, Ishikawa 920-0293, Japan.
Daisuke
D
Koya
Department of Medicine, Shiga University of Medical Science, Tsukinowa-Cho, Seta, Otsu, Shiga 520-2192, Japan.
Hiroshi
H
Maegawa
Department of Medicine, Shiga University of Medical Science, Tsukinowa-Cho, Seta, Otsu, Shiga 520-2192, Japan.
Takashi
T
Uzu
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000503:physiopathology; D055808:Drug Discovery; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000502:physiology; D050199:Podocytes / Q000502:physiology