Kume Shinji, Koya Daisuke
Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Department of Diabetology & Endocrinology, Kanazawa Medical University, Kahoku, Japan.
Diabetes Metab J. 2015 Dec;39(6):451-60. doi: 10.4093/dmj.2015.39.6.451.
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.
糖尿病肾病是终末期肾病的主要病因,其发病率在全球范围内呈上升趋势。针对该病症最有效的治疗策略是强化治疗,即使用肾素 - 血管紧张素系统抑制剂严格控制血糖和血压。然而,即使在这种强化治疗下,仍有一部分患者最终发展至终末期肾病。因此,迫切需要针对糖尿病肾病的新治疗靶点。自噬是哺乳动物细胞降解大分子和细胞器以维持细胞内稳态的主要分解代谢途径。受损蛋白质和细胞器的积累与糖尿病肾病的发病机制有关。肾脏中的自噬在某些应激条件下被激活,如近端肾小管细胞中的氧化应激和缺氧,甚至在足细胞的正常条件下也会发生。这些以及其他不断积累的研究结果导致了一种假说,即自噬参与了糖尿病肾病的发病机制。在此,我们综述支持这一假说的最新研究结果,并讨论针对自噬治疗糖尿病肾病的优势。