Human Umbilical Cord-Derived Mesenchymal Stem Cells-Exosomes-Delivered miR-375 Targets HDAC4 to Promote Autophagy and Suppress T Cell Apoptosis in Sepsis-Associated Acute Kidney Injury.

This study sought to elucidate the mechanism of human umbilical cord-derived mesenchymal stem cells (HUCMSCs)-exosomes (Exos) in sepsis-associated acute kidney injury (SAKI). Exos were isolated from HUCMSCs and co-cultured with CD4+ T cells exposed to lipopolysaccharide to detect the effects of HUCMSCs-Exos on CD4+ T cell apoptosis and autophagy. miR-375 expression in CD4+ T cells and HUCMSCs-Exos was examined. The relationship between miR-375 and HDAC4 was analyzed. A mouse model of SAKI was established and injected with HUCMSCs-Exos to verify the function of HUCMSCs-Exos in vivo. HUCMSCs-Exos inhibited lipopolysaccharide-induced apoptosis of CD4+ T cells and promoted autophagy. miR-375 expression was noted to be elevated in the HUCMSCs-Exos. Importantly, HUCMSCs-Exos could deliver miR-375 into CD4+ T cells where miR-375 targeted HDAC4 and negatively regulated its expression. By this mechanism, HUCMSCs-Exos decreased CD4+ T cell apoptosis and augmented autophagy. This finding was further confirmed in an in vivo SAKI model. Collectively, HUCMSCs-Exos can protect against SAKI via delivering miR-375 that promotes autophagy and arrests T cell apoptosis through HDAC4 downregulation. These findings suggest a promising therapeutic potential for HUCMSCs-Exos in the context of SAKI.