Hypoxia-Induced HIF-1 alpha Expression Promotes Neurogenic Bladder Fibrosis via EMT and Pyroptosis

作者全名："Li, Qi; Hong, Yifan; Chen, Jing; Zhou, Xiazhu; Tian, Xiaomao; Yu, Yihang; Shen, Lianju; Long, Chunlan; Cai, Miao; Wu, Shengde; Wei, Guanghui"

作者地址："[Li, Qi; Hong, Yifan; Chen, Jing; Zhou, Xiazhu; Tian, Xiaomao; Yu, Yihang; Cai, Miao; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Li, Qi; Hong, Yifan; Chen, Jing; Zhou, Xiazhu; Tian, Xiaomao; Yu, Yihang; Shen, Lianju; Long, Chunlan; Cai, Miao; Wu, Shengde; Wei, Guanghui] Minist Educ Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,China Int Sci & Technol C, Chongqing 400014, Peoples R China"

通信作者："Wu, SD; Wei, GH (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China.; Wu, SD; Wei, GH (通讯作者)，Minist Educ Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,China Int Sci & Technol C, Chongqing 400014, Peoples R China."

来源：CELLS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000896938700001

JCR分区：Q2

影响因子：6

年份：2022

卷号：11

期号：23

开始页：　

结束页：　

文献类型：Article

关键词：spinal cord injury; bladder function; fibrosis; HIF-1 alpha; pyroptosis

摘要："Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1 alpha and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1 alpha knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1 alpha pathway. Inhibition of the HIF-1 alpha pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI."

基金机构："National Clinical Research Center for Child Health, General Program of Clinical Research; [NCRCCHD-2020-GP-04]"

基金资助正文："This research was funded by the National Clinical Research Center for Child Health, General Program of Clinical Research, grant number NCRCCHD-2020-GP-04."