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. Myofibroblasts proliferation and microvascular damage are two important events of RIF and pericyte is one of the major sources of myofibroblasts in kidney. However, the underlying mechanisms remain poorly characterized. Here we present that core fucosylation (CF), a posttranslational modification of proteins, is essential for pericyte activation via regulating of profibrotic and antifibrotic signaling pathway as a “hub-like” target. Exosomes deriving from MSCs specifically reside in obstructed kidney and deliver microRNA34c-5p to inhibit CF resulting in reducing pericyte activation and renal fibrosis. Furthermore, we clarify that the ligands and receptors (CD81-EGFR) complex assists the entrance of exosomal microRNA34c-5p into pericytes. Our results reveal a novel mechanism of pericyte activation base on CF and suggest a potential use of MSCs exosome as a new therapeutic strategy for renal interstitial fibrosis through inhibiting CF, the “hub-like” target of profibrotic signaling activation.

ORGANISM(S): Mus Musculus

SUBMITTER: Hongli Lin  

PROVIDER: PXD022358 | iProX | Wed Nov 04 00:00:00 GMT 2020

REPOSITORIES: iProX