Yasuda-Yamahara Mako, Kume Shinji, Tagawa Atsuko, Maegawa Hiroshi, Uzu Takashi
a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
Autophagy. 2015;11(12):2385-6. doi: 10.1080/15548627.2015.1115173.
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.
肾小球足细胞在维持肾小球滤过屏障功能中起关键作用。由于严重的足细胞损伤会导致糖尿病肾病患者出现蛋白尿，确定足细胞损伤的发病机制可能有助于开发新的治疗方法。我们最近发现自噬参与了糖尿病相关足细胞损伤的发病机制。在有大量蛋白尿的糖尿病患者中观察到足细胞自噬不足和足细胞丢失。在高脂饮食诱导的具有足细胞特异性自噬缺陷的糖尿病小鼠中会出现足细胞丢失和大量蛋白尿，这些小鼠以及糖尿病大鼠的足细胞有巨大的受损溶酶体。来自糖尿病患者和有大量蛋白尿的啮齿动物的血清会导致自噬不足，从而导致溶酶体功能障碍和培养的足细胞凋亡。这些发现表明自噬在糖尿病条件下维持足细胞溶酶体稳态中的重要性。自噬受损可能参与了足细胞丢失的发病机制，导致糖尿病肾病中的大量蛋白尿。
