Hypoxia-Inducible Factor 1 alpha Stability Modified by Glutaredoxin-1 in Necrotizing Enterocolitis

作者全名："Zhang, Yunfei; Zhang, Xiao; Tian, Bing; Deng, Qin; Guo, Chunbao"

作者地址："[Zhang, Yunfei; Zhang, Xiao; Tian, Bing; Deng, Qin; Guo, Chunbao] Chongqing Med Univ, Women & Childrens Hosp, Dept Pediat Surg, Chongqing, Peoples R China; [Zhang, Yunfei; Zhang, Xiao; Tian, Bing; Deng, Qin; Guo, Chunbao] Chongqing Med Univ, Childrens Hosp, Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Guo, Chunbao] Chongqing Med Univ, Childrens Hosp, Dept Burn, Chongqing, Peoples R China; [Guo, Chunbao] Chongqing Hlth Ctr Women & Children, Dept Pediat Surg, Chongqing, Peoples R China; [Guo, Chunbao] Chongqing Med Univ, Women anf Childrens Hosp, Dept Pediat Surg, 120 Longshan Rd, Chongqing 400014, Peoples R China"

通信作者："Guo, CB (通讯作者)，Chongqing Med Univ, Women anf Childrens Hosp, Dept Pediat Surg, 120 Longshan Rd, Chongqing 400014, Peoples R China."

来源：JOURNAL OF SURGICAL RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000864472000021

JCR分区：Q2

影响因子：2.2

年份：2022

卷号：280

期号：　

开始页：429

结束页：439

文献类型：Article

关键词：Glutaredoxin-1; Hypoxia-inducible factor; Intestinal microvasculature; Necrotizing enterocolitis; Vascular endothelial growth factor

摘要："Introduction: Hypoxia-inducible factor (HIF) 1 alpha is essential for the pathogenesis of necrotizing enterocolitis (NEC). HIF-1 alpha is stabilized by glutaredoxin-1 (Grx1) deletion. The precise role of HIF-1 alpha in the intestinal microcirculation in NEC is not well defined. We aimed to determine the role of HIF-1 alpha in the regulation of the intestinal microcirculation during the development of NEC. Methods: Experimental NEC was induced in full-term C57BL/6 mice and Grx1(-/-)pups through the formula gavage and hypoxia technique. HIF-1 alpha signaling was blocked using the HIF-1 alpha inhibitor, YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole]. Intestinal tissues were collected at predetermined time points for the assessment of the intestinal micro-circulation and HIF-1 alpha activity and signaling. Results: We found that NEC induction impaired the intestinal microcirculation, but the impairment of the intestinal blood flow and capillary density was ameliorated in Grx1(-/-)mice. This amelioration was associated with tripeptide glutathione-protein adducts in the intestinal tissue. Grx1 ablation also promoted vascular endothelial growth factor A production in the intestinal tissue. This intestinal microvascular improvement was not found in HIF-1 alpha-inhibited mice, suggesting that HIF-1 alpha was involved in the intestinal microcirculatory perfusion. Conclusions: The current data demonstrated that HIF-1 alpha signaling is involved in the intestinal microvascular modification during the pathogenesis of NEC, suggesting that targeting HIF-1 alpha might be a promising strategy for NEC treatment. (c) 2022 Elsevier Inc. All rights reserved."

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

基金资助正文："This research was supported by the National Natural Sci-ence Foundation of China (grant numbers: 30973440 and 30770950) and the Key Project of the Chongqing Natural Science Foundation (grant numbers: CSTC, 2008BA0021, and cstc2012jjA0155) ."