IL-13 alleviates acute kidney injury and promotes regeneration via activating the JAK-STAT signaling pathway in a rat kidney transplantation model

作者全名："Yu, Chengjun; Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Liu, Zhiyuan; Zhu, Chumeng; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui"

作者地址："[Yu, Chengjun; Tian, Xiaomao; Liu, Zhiyuan; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] Chongqing Med Univ, Dept Urol, Childrens Hosp, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Yu, Chengjun; Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Liu, Zhiyuan; Zhu, Chumeng; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Yu, Chengjun; Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China; [Yu, Chengjun; Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Yu, Chengjun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Yu, Chengjun; Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Zhu, Chumeng; Long, Chunlan; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde; Hua, Yi; Wei, Guanghui] Chongqing Key Lab Pediat Chongqing, Chongqing, Peoples R China; [Wei, Guanghui] Room 806,Kejiao Bldg 6,136,Zhongshan 2nd Rd, Chongqing, Peoples R China; [Zhang, Jie; Pei, Jun; Luo, Jin; Hong, Yifan; Tian, Xiaomao; Liu, Zhiyuan; Zhu, Chumeng; Shen, Lianju; He, Xingyue; Wen, Sheng; Liu, Xing; Wu, Shengde] Chongqing Med Univ, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Wei, GH (通讯作者)，Room 806,Kejiao Bldg 6,136,Zhongshan 2nd Rd, Chongqing, Peoples R China."

来源：LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001178166800001

JCR分区：Q1

影响因子：5.2

年份：2024

卷号：341

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Acute kidney injury; Interleukin-13; Kidney transplantation; Regeneration; Youthful systemic milieu

摘要："Aims: To identify whether and how a younger systemic internal milieu alleviates acute kidney injury (AKI) in grafts after kidney transplantation. Materials and methods: We conducted an allogenic heterotopic rat kidney transplantation model with young and adult recipients receiving similar donor kidneys. We evaluated the renal function, histological damage, apoptosis, dedifferentiation, proliferation, hub regulating cytokines, and signaling pathways involved in young and adult recipients based on transcriptomics, proteomics, and experimental validation. We also validated the protective effect and mechanism of interleukin-13 (IL-13) on tubular epithelial cell injury induced by transplantation in vivo and by cisplatin in vitro. Key findings: Compared with adult recipients, the young recipients had lower levels of renal histological damage and apoptosis, while had higher levels of dedifferentiation and proliferation. Serum IL-13 levels were higher in young recipients both before and after surgery. Pretreating with IL-13 decreased apoptosis and promoted regeneration in injured rat tubular epithelial cells induced by cisplatin, while this effect can be counteracted by a JAK2 and STAT3 specific inhibitor, AG490. Recipients pretreated with IL-13 also had lower levels of histological damage and improved renal function. Significance: Higher levels of IL-13 in young recipients ameliorates tubular epithelial cell apoptosis and promotes regeneration via activating the JAK-STAT signaling pathway both in vivo and in vitro. Our results suggest that IL13 is a promising therapeutic strategy for alleviating AKI. The therapeutic potential of IL-13 in injury repair and immune regulation deserves further evaluation and clinical consideration."

基金机构：Chongqing Municipal Health Commis-sion [2022ZDXM033]

基金资助正文：This work was supported by Chongqing Municipal Health Commis-sion (2022ZDXM033) .