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.

Details

Title
Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17 axis
Author
Shi, Linru 1 ; Hu, Yuyan 2 ; Zeng, Houcheng 3 ; Shi, Hui 3 ; Xu, Wenrong 3 ; Sun, Yaoxiang 4 ; Chu, Hong 4 ; Ji, Cheng 3 ; Qian, Hui 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) 
 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) 
 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) 
 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) 
Pages
17703
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3086483173
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.