The PI3K-AKT-mTOR signaling pathway mediates the cytoskeletal remodeling and epithelial-mesenchymal transition in bladder outlet obstruction

作者全名："Zhang, Zhaoxia; Zhanghuang, Chenghao; Mi, Tao; Jin, Liming; Liu, Jiayan; Li, Maoxian; Wu, Xin; Wang, Jinkui; Li, Mujie; Wang, Zhang; Guo, Peng; He, Dawei"

作者地址："[Zhang, Zhaoxia; Zhanghuang, Chenghao; Mi, Tao; Jin, Liming; Liu, Jiayan; Li, Maoxian; Wu, Xin; Wang, Jinkui; Li, Mujie; Wang, Zhang; Guo, Peng; He, Dawei] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Zhang, Zhaoxia; Zhanghuang, Chenghao; Mi, Tao; Jin, Liming; Liu, Jiayan; Li, Maoxian; Wu, Xin; Wang, Jinkui; Li, Mujie; Wang, Zhang; Guo, Peng] Children Urogenital Dev & Tissue Engn, Chongqing Key Lab, Chongqing 400014, Peoples R China; [Zhang, Zhaoxia; Zhanghuang, Chenghao; Mi, Tao; Jin, Liming; Liu, Jiayan; Li, Maoxian; Wu, Xin; Wang, Jinkui; Li, Mujie; Wang, Zhang; Guo, Peng] Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Zhang, Zhaoxia; Zhanghuang, Chenghao; Mi, Tao; Jin, Liming; Liu, Jiayan; Li, Maoxian; Wu, Xin; Wang, Jinkui; Li, Mujie; Wang, Zhang; Guo, Peng] Chongqing Key Lab Pediat, Key Lab Child Dev & Disorders, Minist Educ, Chongqing 400014, Peoples R China; [Guo, Peng] Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China; [Zhanghuang, Chenghao] Kunming Med Univ, Dept Urol, Childrens Hosp, Kunming 650103, Yunnan, Peoples R China"

通信作者："He, DW (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001110007000001

JCR分区：Q1

影响因子：3.4

年份：2023

卷号：9

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：pBOO; Fibrosis; EMT; Cytoskeleton; Remodeling

摘要："Objective: Partial bladder outlet obstruction(pBOO) is the most common cause of lower urinary tract symptoms (LUTS) and significantly affects the quality of life. Long-term pBOO can cause changes in bladder structure and function, referred to as bladder remodeling. The pathogenesis of pBOO-induced bladder remodeling has yet to be fully understood, so effective treatment options are lacking. Our study aimed to explore how pBOO-induced bladder remodeling brings new strategies for treating pBOO. Methods: A rat model of pBOO was established by partial ligation of the bladder neck, and the morphological changes and fibrosis changes in the bladder tissues were detected by H&E and Masson trichrome staining. Furthermore, EMT(epithelial-mesenchymal transition) related indicators and related pathway changes were further examined after TGF- beta treatment of urothelial cells SV-HUC-1. Finally, the above indicators were tested again after using the PI3K inhibitor. Subsequently, RNA sequencing of bladder tissues to identify differential genes and related pathways enrichment and validated by immunofluorescence and western blotting analysis. Results: The pBOO animal model was successfully established by partially ligating the bladder neck. H&E staining showed significant changes in the bladder structure, and Masson trichrome staining showed significantly increased collagen fibers. RNA sequencing results significantly enriched in the cytoskeleton, epithelial-mesenchymal transformation, and the PI3K-AKT-mTOR signaling pathway. Immunofluorescence and western blotting revealed EMT and cytoskeletal remodeling in SV-HUC-1 cells after induction of TGF- beta and in the pBOO bladder tissues. The western blotting showed significant activation of the PI3K-AKT-mTOR signaling pathway in SV HUC-1 cells after induction of TGF-beta and in pBOO bladder tissues. Furthermore, EMT and cytoskeletal damage were partially reversed after PI3K pathway inhibition using PI3K inhibitors. Conclusions: In the pBOO rat model, the activation of the PI3K-AKT-mTOR signaling pathway can mediate the cytoskeletal remodeling and the EMT to induce fibrosis in the bladder tissues. PI3K inhibitors partially reversed EMT and cytoskeletal damage."

基金机构：Chongqing Talent Program"lump sum project" [cstc2021ycjh-bgzxm0253]; Science and Technology Innovation Key R&D Program of Chongqing [CSTB2022TIAD-STX0013]

基金资助正文：<B>Funding</B> Chongqing Talent Program"lump sum project" (cstc2021ycjh-bgzxm0253) . Science and Technology Innovation Key R&D Program of Chongqing (CSTB2022TIAD-STX0013) .