足细胞
基因敲除
狭缝隔膜
基因剔除小鼠
癌症研究
细胞凋亡
糖尿病肾病
生物
肾
细胞生物学
内分泌学
受体
生物化学
蛋白尿
作者
Yingying Zhang,Chengxian Xu,Qing Ye,Lingxiao Tong,Hong Jiang,Xiujuan Zhu,Li‐Min Huang,Weiqiang Lin,Haidong Fu,Jingjing Wang,Pontus B. Persson,En Yin Lai,Jianhua Mao
摘要
Abstract Aims Diabetic nephropathy (DN) is a leading cause of end‐stage renal disease. BASP1 (brain acid‐soluble protein) is up‐regulated in podocyte‐specific protein phosphatase 2A knockout mice (Pod‐PP2A‐KO) that develop kidney dysfunction. Here, we explore the role of BASP1 for podocytes in DN. Methods BASP1 was assessed in kidneys from DN patients and DN mouse models, podocyte specific BASP1 knockout mice (Pod‐BASP1‐KO mice) were generated and studied in vivo. Furthermore, podocyte injury and apoptosis were measured after BASP1 knockdown and overexpression in a mouse podocyte cell line (MPC5). Potential signalling pathways involved in podocyte apoptosis were detected. Results BASP1 expression was up‐regulated in DN patients compared to normal controls. BASP1 specific deletion in podocytes protected against podocyte injury by reducing the loss of expression of slit diaphragm molecules and foot process effacement in the DN model. BASP1 promoted actin cytoskeleton rearrangements and apoptosis in the MPC5 podocyte line. Molecules involved in the p53 pathway were down‐regulated in BASP1 knockdown podocytes treated with high glucose compared to controls. BASP1 promoted podocyte apoptosis and P53 pathway activation through co‐repression with Wilms' tumour 1 transcription factor (WT1). Conclusion BASP1 activates the p53 pathway through modulation of WT1 to induce podocyte apoptosis in diabetic nephropathy.
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