上睑下垂
链脲佐菌素
凝集素
细胞生物学
足细胞
肾
糖尿病
化学
炎症
内分泌学
内科学
癌症研究
医学
细胞凋亡
生物
炎症体
生物化学
蛋白尿
作者
Fengfan Zheng,Linqiang Ma,Xuan Li,Rufei Gao,Chuan Peng,Bing Kang,Yue Wang,Ting Luo,Jinshan Wu,Yi Yang,Lilin Gong,Qifu Li,Sen Yang,Jinbo Hu
出处
期刊:Diabetes
[American Diabetes Association]
日期:2022-09-12
卷期号:71 (12): 2739-2750
被引量:26
摘要
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Neutrophil extracellular traps (NETs) are a network structure composed of loose chromatin and embedded with multiple proteins. Here, we observed increased NETs deposition in the glomeruli of DKD patients and diabetic mice (streptozotocin-induced or db/db mice). After NETs were degraded with DNase I, diabetic mice exhibited attenuated glomerulopathy and glomerular endothelial cells (GECs) injury. We also observed alleviated glomerulopathy and GECs injury in peptidylarginine deiminase 4-knockout mice with streptozotocin-induced diabetes. In vitro, NETs-induced GECs pyroptosis was characterized by pore formation in the cell membrane, dysregulation of multiple genes involved in cell membrane function, and increased expression of pyroptosis-related proteins. Strengthening the GECs surface charge by oleylamine significantly inhibited NETs-induced GECs pyroptosis. These findings suggest that the GECs charge-related pyroptosis is involved in DKD progression, which is promoted by NETs.
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