Mesenchymal Stem Cell-derived Extracellular Vesicles Ameliorate Renal Interstitial Fibrosis Via the MiR-13474/ADAM17 Axis

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jul 31

PMID 39085289

Authors

Linru Shi

Yuyan Hu

Houcheng Zeng

Hui Shi

Wenrong Xu

Yaoxiang Sun

Hong Chu

Cheng Ji

Hui Qian

Affiliations

Soon will be listed here.

Abstract

Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-β signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-β signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.

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