Mesenchymal cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury

被引:0
|
作者
Huang, Jing [1 ]
Shi, Lang [4 ]
Yang, Yifei [1 ]
Zhao, Fan [1 ]
Chen, Rengui [1 ]
Liao, Wenliang [1 ]
Zhu, Jiefu [2 ]
Yang, Dingping [1 ]
Wu, Xiongfei [3 ]
Han, Shangting [2 ]
机构
[1] Wuhan Univ, Dept Nephrol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Organ Transplantat, Wuhan 430060, Hubei, Peoples R China
[3] Guiqian Int Gen Hosp, Dept Nephrol, Guiyang, Guizhou, Peoples R China
[4] Lanzhou Univ, Hosp 1, Dept Nephrol, Lanzhou 730000, Peoples R China
关键词
Mesenchymal stem cell exosomes; Renal ischemia reperfusion injury; Renal fibrosis; Vascular rarefaction; microRNA; DIABETIC-NEPHROPATHY;
D O I
10.1186/s13287-025-04226-4
中图分类号
Q813 [细胞工程];
学科分类号
摘要
BackgroundRenal fibrosis and vascular rarefaction are significant complications of ischemia/reperfusion (I/R) injury. Human umbilical cord mesenchymal cell-derived exosomes (hucMSC-exos) have shown potential in mitigating these conditions. This study investigates the role of miR-29a-3p in exosomes and its therapeutic effects on I/R-induced renal damage.MethodsMale C57BL/6 mice were subjected to unilateral renal ischemia for 28 min followed by reperfusion. Exosomes and miR-29a-3p mimics/inhibitors were injected into the mice. Renal function, histological analysis, and molecular assays were performed to evaluate fibrosis and vascular integrity.ResultsExosome treatment significantly improved renal function and reduced fibrosis and vascular rarefaction post-I/R. MiR-29a-3p was highly expressed in hucMSC-exos but reduced in renal fibrosis models. MiR-29a-3p mimic reduced, while its inhibitor exacerbated I/R-induced renal fibrosis and vascular rarefaction. Collagen I and TNFR1 were identified as direct targets of miR-29a-3p in fibroblasts and endothelial cells, respectively. Exosomes overexpressing miR-29a-3p provided superior protection compared to unmodified hucMSC-exos.ConclusionHucMSC-exos, particularly those overexpressing miR-29a-3p, have potent therapeutic effects against renal fibrosis and vascular rarefaction post-I/R. MiR-29a-3p targets TNFR1 and collagen I, highlighting its potential in renal fibrosis therapy.
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页数:17
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