Extracellular vesicles secreted from mesenchymal stem cells ameliorate renal ischemia reperfusion injury by delivering miR-100-5p targeting FKBP5/AKT axis

作者全名："Chen, Guo; Li, Xinyuan; Zhou, Xiang; Li, Yang; Yu, Haitao; Peng, Xiang; Bai, Xuesong; Zhang, Chunlin; Feng, Zhenwei; Mei, Yuhua; Li, Li; Liu, Yu; Gou, Xin; Jiang, Yuanbin"

作者地址："[Chen, Guo; Li, Xinyuan; Zhou, Xiang; Li, Yang; Yu, Haitao; Peng, Xiang; Bai, Xuesong; Zhang, Chunlin; Feng, Zhenwei; Mei, Yuhua; Li, Li; Gou, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400000, Peoples R China; [Liu, Yu; Jiang, Yuanbin] Chongqing Tradit Chinese Med Hosp, Dept Urol, 6 Panxi Rd,Branch 7, Chongqing 400021, Peoples R China; [Chen, Guo; Li, Xinyuan; Zhou, Xiang; Li, Yang; Yu, Haitao; Peng, Xiang; Bai, Xuesong; Zhang, Chunlin; Feng, Zhenwei; Mei, Yuhua; Li, Li; Liu, Yu; Gou, Xin; Jiang, Yuanbin] Chongqing Key Lab Mol Oncol & Epigenet, Chongqing 400000, Peoples R China"

通信作者："Jiang, YB (通讯作者)，Chongqing Tradit Chinese Med Hosp, Dept Urol, 6 Panxi Rd,Branch 7, Chongqing 400021, Peoples R China.; Jiang, YB (通讯作者)，Chongqing Key Lab Mol Oncol & Epigenet, Chongqing 400000, Peoples R China."

来源：SCIENTIFIC REPORTS

ESI学科分类：Multidisciplinary

WOS号：WOS:001192455600054

JCR分区：Q1

影响因子：3.8

年份：2024

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Human umbilical cord mesenchymal stem cells; Small extracellular vesicles; miR-100-5p; FKBP5; Ischemia-reperfusion injury; Apoptosis

摘要："The incidence of acute kidney injury (AKI) due to ischemia-reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI."

基金机构：Joint project of Chongqing Health Commission and Science and Technology Bureau [2023MSXM083]; Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau)

基金资助正文：This study was supported by the Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) No. 2023MSXM083.