MSCs-derived HGF alleviates senescence after AKI by modulating mitoSTAT3-controlled copper flux and respiration.

ABSTRACT:

Background

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.

Methods

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 u

SUBMITTER: Zhuang K 

PROVIDER: S-EPMC12482249 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature