Inhibition of the NF-kappa B Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis

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

作者地址："[Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China; [Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China; [Chen, Jing; Li, Qi; Hong, Yifan; Zhou, Xiazhu; Yu, Chengjun; Tian, Xiaomao; Zhao, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] China Int Sci & Technol Cooperat Base Child Dev &, 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)，Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China.; Wu, SD; Wei, GH (通讯作者)，Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China.; Wu, SD; Wei, GH (通讯作者)，Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China.; Wu, SD; Wei, GH (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China.; Wu, SD; Wei, GH (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:001032334600001

JCR分区：Q1

影响因子：4.9

年份：2023

卷号：24

期号：13

开始页：　

结束页：　

文献类型：Article

关键词：neurogenic bladder; spinal cord injury; NF-kappa B signaling pathway; pyroptosis; fibrosis

摘要："Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-kappa B signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-kappa B signaling pathway and pyroptosiswere involved in bladder fibrosis, a TGF-beta 1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-kappa B signaling pathway and pyroptosis might play important roles in TGF-beta 1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitorMCC950 rescued TGF-beta 1-induced fibrosis, and the NF-kappa B signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-beta 1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-kappa B signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders."

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."