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.
Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-34c-5p Ameliorates Renal Interstitial Fibrosis by Inhibiting the Core Fucosylation of Multiple Proteins
