Endothelial progenitor cells-secreted extracellular vesicles containing microRNA-93-5p confer protection against sepsis-induced acute kidney injury via the KDM6B/H3K27me3/TNF-α axis.
Abstract
The pivotal pathogenetic role of microRNAs (miRs) in sepsis-induced acute kidney injury (AKI) has been demonstrated in mounting evidence. The functions of the target cells are regulated through the release of cells-encapsulated extracellular vesicles (Evs) into the extracellular space. The present study aims to elucidate the clinical significance as well as biological function of the endothelial progenitor cell (EPC)-derived Evs containing miR-93-5p in sepsis-induced AKI. We first established a cellular sepsis-induced AKI mouse model by treatment with lipopolysaccharide (LPS), and tested ectopic expression and depletion experiments in the model. Evs derived from miR-93-5p inhibitor-transfected EPCs (Evs/miR-93-5p inhibitor) were isolated, and co-cultured with HK2 cells to explore the effects of EPC-derived Evs overexpressing miR-93-5p on LPS-induced HK2 cell injury. The interaction between miR-93-5p and lysine (K)-specific demethylase 6B (KDM6B) was identified using dual-luciferase reporter assay, and ChIP was used to validate the relationship between KDM6B and tumor necrosis factor-α (TNF-α). Mice were made septic by cecal ligation and puncture (CLP), and then injected with Ev/miR-93-5p inhibitor to explore its functions in vi...Continue Reading
References
A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury
Citations
LncRNA KCNQ1OT1 promotes the development of diabetic nephropathy by regulating miR-93-5p/ROCK2 axis.
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