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- Title
Neutrophil Extracellular Traps Induce Glomerular Endothelial Cell Dysfunction and Pyroptosis in Diabetic Kidney Disease.
- Authors
Zheng, Fengfan; Ma, Linqiang; Li, Xuan; Wang, Zhihong; Gao, Rufei; Peng, Chuan; Kang, Bing; Wang, Yue; Luo, Ting; Wu, Jinshan; Yang, Yi; Gong, Lilin; Li, Qifu; Yang, Shumin; Hu, Jinbo
- Abstract
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.
- Publication
Diabetes, 2022, Vol 71, Issue 12, p2739
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db22-0153