Neutrophil Extracellular Traps Induce Glomerular Endothelial Cell Dysfunction and Pyroptosis in Diabetic Kidney Disease
作者全名："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"
作者地址："[Zheng, Fengfan; Ma, Linqiang; Wang, Zhihong; Wang, Yue; Luo, Ting; Wu, Jinshan; Yang, Yi; Gong, Lilin; Li, Qifu; Yang, Shumin; Hu, Jinbo] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, Chongqing, Peoples R China; [Ma, Linqiang; Peng, Chuan] Chongqing Med Univ, Chongqing Key Lab Translat Med Major Metab Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Xuan; Kang, Bing] Chongqing Med Univ, Dept Clin Nutr, Affiliated Hosp 1, Chongqing, Peoples R China; [Gao, Rufei] Chongqing Med Univ, Sch Publ Hlth & Management, Chongqing, Peoples R China"
通信作者："Li, QF; Yang, SM; Hu, JB (通讯作者)，Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, Chongqing, Peoples R China."
来源：DIABETES
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:000905189200030
JCR分区：Q1
影响因子：7.7
年份：2022
卷号：71
期号：12
开始页：2739
结束页：2750
文献类型：Article
关键词：
摘要："Diabetic kidney disease (DKD) is the leading cause of endstage 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 pyroptosisrelated 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."
基金机构："National Natural Science Foundation of China [81800731, 81870567, 81970720, 82000810, 82170825, 82270878, U21A20355]; China Postdoctoral Science Foundation [2019M663499]; Chongqing Postdoctoral Innovative Talents Support Project [2020[379]]; Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission [2021ZDXM002]; Natural Science Foundation of Chongqing [cstc2020jcyj-bshX0081]; Outstanding Talents of the First Affiliated Hospital of Chongqing Medical University [2019-4-22]; Program for Youth Innovation in Future Medicine, Chongqing Medical University, Chongqing Outstanding Youth Funds [cstc2019jcyjjq0006]; Bethune Merck Diabetes Research Foundation [G2018030]"
基金资助正文："This work was supported by the National Natural Science Foundation of China, Major Joint Project (U21A20355), National Natural Science Foundation of China (81800731, 81870567, 81970720, 82000810, 82170825, and 82270878), the China Postdoctoral Science Foundation (2019M663499), the Chongqing Postdoctoral Innovative Talents Support Project (2020[379]), Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission (Major Project, 2021ZDXM002), the Natural Science Foundation of Chongqing (cstc2020jcyj-bshX0081), Outstanding Talents of the First Affiliated Hospital of Chongqing Medical University 2019 (2019-4-22 for J.H.), Program for Youth Innovation in Future Medicine, Chongqing Medical University, Chongqing Outstanding Youth Funds (cstc2019jcyjjq0006), and Bethune Merck Diabetes Research Foundation (G2018030)."
