Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia

作者全名："Han, Wenli; Zhang, Fengmei; Mo, Dandan; Zhang, Xiao; Chen, Bailin; Ding, Xionghui; Guo, Hongjie; Li, Fang; Guo, Chunbao"

作者地址："[Han, Wenli; Zhang, Fengmei] Chongqing Med Univ, Sch Pharm, Chongqing, Peoples R China; [Han, Wenli; Mo, Dandan; Li, Fang; Guo, Chunbao] Chongqing Hlth Ctr Women & Children, Dept Pediat, Chongqing, Peoples R China; [Han, Wenli; Zhang, Fengmei; Mo, Dandan; Zhang, Xiao; Guo, Hongjie] Chongqing Med Univ, Dept Anim Ctr, Childrens Hosp, Chongqing, Peoples R China; [Zhang, Xiao; Ding, Xionghui] Chongqing Med Univ, Dept Burn, Childrens Hosp, Chongqing, Peoples R China; [Chen, Bailin] Chongqing Med Univ, Dept Gen Surg, Childrens Hosp, Chongqing, Peoples R China; [Li, Fang; Guo, Chunbao] Chongqing Med Univ, Women & Chidrens Hosp, Dept Pediat, Chongqing, Peoples R China; [Li, Fang; Guo, Chunbao] Chongqing Hlth Ctr Women & Children, Dept Pediat, 120 Longshan Rd, Chongqing 401147, Peoples R China"

通信作者："Li, F; Guo, CB (通讯作者)，Chongqing Hlth Ctr Women & Children, Dept Pediat, 120 Longshan Rd, Chongqing 401147, Peoples R China."

来源：CELL BIOLOGY INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000915431400001

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：47

期号：4

开始页：796

结束页：807

文献类型：Article

关键词：BPD; Grx1; HIF-1 alpha; S-glutathionylation; VEGF

摘要："Hypoxia inducible factor (HIF)-1 alpha could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1 alpha by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1 alpha stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1 alpha glutathionylation by increasing GSH adducts to stabilize HIF-1 alpha and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1 alpha inhibitor, suggesting the HIF-1 alpha dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1 alpha stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1 alpha stabilization should be a potential clinical and therapeutic strategy for BPD treatment."

基金机构：National Natural Science Foundation of China [81900001]

基金资助正文："National Natural Science Foundation of China, Grant/Award Number: 81900001"