Diabetes, Metabolic Syndrome and Obesity (Sep 2019)
Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy
Abstract
Tao Wang,1 Yanbin Gao,1,2 Xiaolei Wang,1 Yimin Shi,1 Jiayi Xu,1 Bingjie Wu,1 Jiaxin He,1 Yimeng Li2 1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, People’s Republic of ChinaCorrespondence: Yanbin GaoSchool of Traditional Chinese Medicine, Capital Medical University, No. 10, Youanmenwai, Xitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 108 391 1720Email [email protected]: Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), driven largely by podocyte apoptosis. The cysteine protease Calpain 10 is known to augment apoptosis and necrosis, and is a potential therapeutic target in DN.Methods: Type 2 diabetes was induced in SD rats by high-fat diet (HFD) feeding and streptozotocin (STZ) injections, and simulated in vitro by culturing conditionally immortalized mouse podocytes in hyperlipidemic (PA, 100 μM) conditions. The rate of apoptosis in the renal tissues and cultured podocytes was determined by TUNEL assay. The expression of Calpain 10 and its biological effects were assayed by real-time PCR, Western blotting, immunofluorescence and electron microscopy.Results: Calpain 10 was up-regulated in the kidneys of DN rats, as well as immortalized mouse podocytes. High levels of Calpain 10 was associated with renal dysfunction and tissue destruction, and podocyte injury and apoptosis. Knockdown of Calpain 10 protected podocytes by decreasing apoptosis rate, and upregulated nephrin.Conclusion: Calpain 10 is a pro-apoptotic factor in DN, and can be targeted for treating glomerular diseases.Keywords: Calpain 10, podocyte, apoptosis, diabetic nephropathy
