Mesenchymal stem cell–derived exosomal microRNA-34c-5p ameliorates renal pericyte activation by inhibiting core fucosylation

Abstract Renal interstitial fibrosis (RIF) is an incurable pathological lesion in progressive chronic kidney diseases. Myofibroblast proliferation and microvascular damage are two important events in RIF, and pericytes are a major source of myofibroblasts in the kidney. However, the underlying mechanisms remain poorly characterized. We report that core fucosylation (CF), a post-translational modification of proteins, is essential for pericyte activation by regulating profibrotic and antifibrotic signaling pathways as a “hub-like” target. Mesenchymal stem cell (MSC)-derived exosomes reside specifically in the obstructed kidney and deliver microRNA (miR)-34c-5p to inhibit CF, reducing pericyte activation and renal fibrosis. Furthermore, we clarify that the CD81–EGFR ligand–receptor complex aids the entry of exosomal miR-34c-5p into pericytes. Our results reveal a novel mechanism of pericyte activation based on CF and suggest a potential use of MSC exosomes as a new therapeutic strategy for RIF by inhibiting CF, the hub-like target of profibrotic signaling activation.