MSC-Derived Exosomal MiR-127-3p Alleviates Acute Kidney Ischemia-Reperfusion Injury via Suppressing ATG5/ATG7-Mediated Autophagy.

Abstract

Aim: Mesenchymal stem cell-derived exosome (MSC-exo) has garnered increasing attention because of its therapeutic potential for acute kidney injury (AKI). The aim of this study is to investigate the regulatory mechanism of MSC-exo in ischaemic AKI.

Methods: We first isolated MSC-exo and identified its properties through transmission electron microscopy observation, nanoparticle tracking analysis, PKH26 staining and Western blot analysis of surface markers. We also determined the therapeutic effect of MSC-exo on AKI through establishing an ischemia-reperfusion (I/R) animal model. The cell model was also constructed by hypoxia-reperfusion (H/R) and used for functional assays. Student's t-test and one-way ANOVA were used to analyse the data.

Results: MSC-exo could alleviate the I/R-induced renal injury. In a cell model, MSC-exo could enhance proliferation, reduce apoptosis and block autophagy. Subsequently, miR-127-3p was determined to be transmitted by MSC-exo into injured renal cells to alleviate renal cell injury. Mechanism investigation revealed that miR-127-3p could directly target KIF3B to inactivate the Gli1-hedgehog pathway and thus transcriptionally inactivate ATG5 and ATG7.

Conclusion: MiR-127-3p transmitted by MSC-exo alleviates renal cell injury in AKI by suppressing ATG5/ATG7-mediated autophagy. This study explored a new molecular pathway associated with the therapeutic effect of MSC-exo on AKI, which might highlight the MSC-based therapeutic strategy for AKI.