Ma Ping, Shao Hailin, Xu Donghong, Qi Xiaoyu
Department of Endocrinology, Tianjin 4th Center Hospital, Tianjin, 300140, China.
J Bioenerg Biomembr. 2025 Feb;57(1):49-55. doi: 10.1007/s10863-024-10049-4. Epub 2025 Jan 4.
To investigate the role of silent information regulator 6 (SIRT6) in regulating podocyte injury in diabetic nephropathy (DN) through autophagy mediated by Notch signaling pathway. A blank control group (group A), a diabetic nephropathy group (group B), and a Sirt6 intervention group (group C) were established. The group A cells were human normal glomerular podocyte cell lines (HGPCs) without any treatment. In group B, the cells were cultivated in glucose medium containing 30 mmol/L and a 10 µmol/L anti-LSirt6 antibody solution. Three sets of cells were tested for their capacity to proliferate via CCK8, for protein expression via Western blot, for associated mRNA expression levels via qPCR, and for cell migration and invasion ability via Transwell. The podocyte proliferation and migration activity in group B were reduced compared to group A, while these properties in group C were elevated compared to group B (DN). B Group is diabetes nephropathy. Compared with those in group B, the number of invading podocytes in group C were greater than those in group A, and the overall apoptosis rate in group C was lower than that in group B. The expression levels of apoptotic proteins in the podocytes in group C were greater than those in group B, and the bcl-2 level was lower than those in group B. The Notch1 and Jagged1 mRNA and protein levels in the podocytes in group B were greater than those in group A, whereas those in the podocytes in group C were lower than those in group B. Sirt6 can protect against podocyte autophagy injury in DN by regulating the Notch1 signaling pathway.
探讨沉默信息调节因子6（SIRT6）通过Notch信号通路介导的自噬在调节糖尿病肾病（DN）足细胞损伤中的作用。设立空白对照组（A组）、糖尿病肾病组（B组）和Sirt6干预组（C组）。A组细胞为人正常肾小球足细胞系（HGPCs），未进行任何处理。B组细胞在含30 mmol/L葡萄糖的培养基和10 µmol/L抗LSirt6抗体溶液中培养。通过CCK8检测三组细胞的增殖能力，通过蛋白质印迹法检测蛋白质表达，通过qPCR检测相关mRNA表达水平，通过Transwell检测细胞迁移和侵袭能力。与A组相比，B组足细胞增殖和迁移活性降低，而与B组（糖尿病肾病组）相比，C组这些特性升高。B组为糖尿病肾病组。与B组相比，C组侵袭足细胞数量多于A组，C组总体凋亡率低于B组。C组足细胞中凋亡蛋白表达水平高于B组，bcl-2水平低于B组。B组足细胞中Notch1和Jagged1 mRNA及蛋白水平高于A组，而C组足细胞中Notch1和Jagged1 mRNA及蛋白水平低于B组。Sirt6可通过调节Notch1信号通路保护糖尿病肾病足细胞免受自噬损伤。
