biostudies-literatureZhuang KNatural Science Foundation of Beijing MunicipalityNational Natural Science Foundation of ChinaChina Postdoctoral Science Foundation526https://www.ebi.ac.uk/biostudies/studies/S-EPMC12482249biostudies-literatureUnknown16(1)<h4>Background</h4>Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can reverse senescence after acute kidney injury (AKI) via maintaining mitochondrial homeostasis. Copper accumulation and STAT3 nuclear translocation promote senescence, but their mitochondrial localization in response to MSCs remains unclear.<h4>Methods</h4>C57 mice with renal unilateral ischemia reperfusion injury (uIRI) were renal capsular transplanted with hUC-MSCs for two weeks to assessed treatment efficacy. Then, RNA sequencing, protein co-immunoprecipitation, molecular docking, and molecular dynamic simulation were used to found the relationship between senescence, mitochondrial translocation of STAT3 (mitoSTAT3), and copper homeostasis. Furthermore, inhibition of cMet/HGFR, mitoSTAT3, or COX17 were uStem cell research & therapyMSCs-derived HGF alleviates senescence after AKI by modulating mitoSTAT3-controlled copper flux and respiration.PMC12482249821706862024M7542887254312No. 82200762Zheng XFeng ZWang SZhang YLiang YXu CWang WChen YChen XZhuang KCai GfalseMSCs-derived HGF alleviates senescence after AKI by modulating mitoSTAT3-controlled copper flux and respiration.<h4>Background</h4>Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can reverse senescence after acute kidney injury (AKI) via maintaining mitochondrial homeostasis. Copper accumulation and STAT3 nuclear translocation promote senescence, but their mitochondrial localization in response to MSCs remains unclear.<h4>Methods</h4>C57 mice with renal unilateral ischemia reperfusion injury (uIRI) were renal capsular transplanted with hUC-MSCs for two weeks to assessed treatment efficacy. Then, RNA sequencing, protein co-immunoprecipitation, molecular docking, and molecular dynamic simulation were used to found the relationship between senescence, mitochondrial translocation of STAT3 (mitoSTAT3), and copper homeostasis. Furthermore, inhibition of cMet/HGFR, mitoSTAT3, or COX17 were u2025-01-01T00:00:00Z2025 Sep2026-07-15T09:49:53.62Z2026-07-02T03:12:13.417ZS-EPMC124822494102428210.1186/s13287-025-04653-3