HucMSC exosomes attenuate partial bladder outlet obstruction-induced renal injury and cell proliferation via the Wnt/beta-catenin pathway

作者全名："Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei"

作者地址："[Wei, Guanghui; He, Dawei] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China; [Liu, Bo] Chongqing Med Univ, Dept Cardiothorac Surg, Childrens Hosp, Chongqing 400014, Peoples R China; [Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei] Children Urogenital Dev & Tissue Engn, Chongqing Key Lab, Chongqing 400014, Peoples R China; [Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei] Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China; [Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China; [Wang, Zhaoying; Yu, Yihang; Jin, Liming; Tan, Xiaojun; Liu, Bo; Zhang, Zhaoxia; Wang, Zhang; Long, Chunlan; Shen, Lianju; Wei, Guanghui; He, Dawei] Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China"

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

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001024835600001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：952

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Partial bladder outlet obstruction; Kidney injury; Chronic kidney disease; Mesenchymal stem cells; Exosomes; Wnt/beta-catenin signaling pathway

摘要："Bladder outlet obstruction (BOO) can cause serious complications including kidney damage; nevertheless, there are currently no animal models for studying BOO-induced kidney damage. Mesenchymal stem cells (MSCs) are widely used in therapeutic studies of renal fibrosis. However, MSC-derived exosomes show improved safety profile and more controllable characteristics compared with those of MSCs. Herein, we established a kidney injury mouse model of partial bladder outlet obstruction (PBOO) and evaluated the effects of human umbilical cord MSC-derived exosomes (hucMSC-Exos) on PBOO-induced reflux kidney injury in this model. Exosomes were isolated from a hucMSC-conditioned medium, purified by ultracentrifugation, and examined. Living image was performed to indicate the distribution of hucMSC-Exos. The PBOO-treated mice interacted with PBS (phosphate-buffered saline) or hucMSC-Exos. Morphologic changes and expression of interstitial-fibrosis-related, cell proliferation and Wnt/beta-catenin signaling-pathway indices were evaluated. At 7 days after induction of PBOO, structural destruction of renal tubules was observed. Expression of the interstitial markers and the cellular-proliferation index increased significantly in the PBOO group compared with the control group. The isolated exosomes were 30-150 nm in diameter, showing a round shape and bilayer membrane structure with CD63, TSG101, Alix expressed, enriched in the kidney of the PBOO group. Administering hucMSC-Exos to post-PBOO mice reversed renal injury and suppressed expression of Wnt/beta-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/beta-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis."

基金机构：Technology Innovation and Application Development of Chongqing Science and Technology Bureau (key project) [cstc2019jscx-tjsbX0003]

基金资助正文：This work was supported by the Technology Innovation and Application Development of Chongqing Science and Technology Bureau (key project) (Grant No. cstc2019jscx-tjsbX0003) .