Glutaredoxin-1 modulates the NF-kB signaling pathway to activate inducible nitric oxide synthase in experimental necrotizing enterocolitis

作者全名：Zhang, Yunfei; Yan, Mei; Xia, Yingying; Yue, Yingbin; Wang, Shuli; Hu, Yuhui; Lai, Genjian; Wu, Quanjiang; Liu, Qianyang; Ding, Xin; Guo, Chunbao

作者地址：[Zhang, Yunfei; Yan, Mei; Yue, Yingbin] Xinjiang Med Univ, Affiliated Hosp 1, Pediat Ctr, Urumqi 830054, Xinjiang, Peoples R China; [Zhang, Yunfei; Wang, Shuli; Hu, Yuhui; Lai, Genjian; Wu, Quanjiang] Renshou Peoples Hosp, Dept Gastrointestinal Surg, Meishan, Sichuan, Peoples R China; [Xia, Yingying; Wang, Shuli; Hu, Yuhui; Lai, Genjian; Wu, Quanjiang; Liu, Qianyang; Ding, Xin; Guo, Chunbao] Chongqing Med Univ, Women & Childrens Hosp, Dept Pediat Surg, Chongqing, Peoples R China; [Liu, Qianyang; Ding, Xin; Guo, Chunbao] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Childrens Hosp, Chongqing, Peoples R China; [Liu, Qianyang; Ding, Xin; Guo, Chunbao] Chongqing Hlth Ctr Women & Children, Dept Pediat Surg, Chongqing, Peoples R China; [Xia, Yingying] Xinjin Dist Second Peoples Hosp, Dept Psychiat, Chengdu, Sichuan, Peoples R China

通信作者：Guo, CB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Pediat Surg, Chongqing, Peoples R China.

来源：MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001205863600001

JCR分区：Q2

影响因子：4.6

年份：2024

卷号：32

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Inducible nitric oxide synthase (iNOS), regulated by nuclear factor kappa B (NF-kB), is crucial for intestinal inflammation and barrier injury in the progression of necrotizing enterocolitis (NEC). The NF-kB pathway is inhibited by S-glutathionylation of inhibitory kB kinase b (IKKb), which can be restored by glutaredoxin-1 (Grx1). Thus, we aim to explore the role of Grx1 in experimental NEC. Wild -type (WT) and Grx1-knockout (Grx1-/-) mice were treated with an NEC -inducing regimen. Primary intestinal epithelial cells (IECs) were subjected to LPS treatment. The production of iNOS, NO, and inflammation injuries were assessed. NF-kB and involved signaling pathways were also explored. The severity of NEC was attenuated in Grx1-/- mice. Grx1 ablation promoted IKKb glutathionylation, NF-kB inactivation, and decreased iNOS, NO, and O2.- production in NEC mice. Furthermore, Grx1 ablation restrained proinflamma- tory cytokines and cell apoptosis, ameliorated intestinal barrier damage, and promoted proliferation in NEC mice. Grx1 ablation protected NEC through iNOS and NO inhibition, which related to S-glutathionylation of IKKb to inhibit NF-kB signaling. Grx1-related signaling pathways provide a new therapeutic target for NEC.

基金机构：National Natural Science Foundation of China [30973440, 30770950]; Key Project of the Chongqing Natural Science Foundation (CSTC) [cstc2012jjA0155, 2008BA0021]

基金资助正文：All of the experiments were approved by the IACUC of Chongqing Medical University. All of the methods performed in the study were carried out in accordance with the approved guidelines and regulations. The study is reported in accordance with the ARRIVE guidelines. This research was supported by the National Natural Science Foundation of China (grant nos. 30973440 and 30770950) and the Key Project of the Chongqing Natural Science Foundation (grant nos. CSTC, 2008BA0021 and cstc2012jjA0155) .