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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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1 The Affiliated Yixing Hospital of Jiangsu University, Center for Molecular & Imageology of Jiangsu University, Division of Nephrology, Yixing, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X); Jiangsu University, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X)
2 Jiangsu University, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X); Shaoxing Central Hospital Medical Alliance General Hospital, The Department of Laboratory, Shaoxing, China (GRID:grid.440785.a)
3 Jiangsu University, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X)
4 The Affiliated Yixing Hospital of Jiangsu University, Center for Molecular & Imageology of Jiangsu University, Division of Nephrology, Yixing, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X)