Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

作者全名："Yu, Yihang; Chen, Meiling; Guo, Qitong; Shen, Lianju; Liu, Xing; Pan, Jianbo; Zhang, Yuanyuan; Xu, Tao; Zhang, Deying; Wei, Guanghui"

作者地址："[Yu, Yihang; Chen, Meiling; Guo, Qitong; Shen, Lianju; Liu, Xing; Zhang, Deying; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Yu, Yihang; Chen, Meiling; Guo, Qitong; Shen, Lianju; Liu, Xing; Zhang, Deying; Wei, Guanghui] China Int Sci & Technol Cooperat Base Child Dev &, Key Lab Child Dev & Disorders, Minist Educ, Chongqing Key Lab Children Urogenital Dept & Tissu, Chongqing 400014, Peoples R China; [Yu, Yihang; Chen, Meiling; Guo, Qitong; Shen, Lianju; Liu, Xing; Zhang, Deying; Wei, Guanghui] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Pan, Jianbo] Chongqing Med Univ, Inst Life Sci, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China; [Zhang, Yuanyuan] Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27101 USA; [Xu, Tao] Tsinghua Univ, Biomfg Ctr, Dept Mech Engn, Beijing 100084, Peoples R China"

通信作者："Zhang, DY (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China.; Zhang, DY (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Key Lab Child Dev & Disorders, Minist Educ, Chongqing Key Lab Children Urogenital Dept & Tissu, Chongqing 400014, Peoples R China.; Zhang, DY (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China."

来源：CELLULAR & MOLECULAR BIOLOGY LETTERS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000928633100001

JCR分区：Q1

影响因子：8.3

年份：2023

卷号：28

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Human umbilical cord mesenchymal stem cells; Exosome; Necroptosis; Mitochondrial fusion; miR-874-3p; Kidney tubular epithelial cell damage

摘要："BackgroundKidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury.MethodsC57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics.ResultsHucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p.ConclusionThe collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage."

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