IMR Press / FBL / Volume 27 / Issue 1 / DOI: 10.31083/j.fbl2701017
Open Access Original Research
Bone marrow mesenchymal stem cell-derived exosomes improve renal fibrosis via regulating Smurf 2/Smad 7
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1 Department of Nephrology, Faculty of Kidney Diseases, Beijing Friendship Hospital, Capital Medical University, 100050 Beijing, China
2 Department of Nephrology, Faculty of Kidney Diseases, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, 100043 Beijing, China

These authors contributed equally.
Academic Editor: Graham Pawelec

Front. Biosci. (Landmark Ed) 2022 , 27(1), 1; https://doi.org/10.31083/j.fbl2701017
Submitted: 30 July 2021 | Revised: 29 November 2021 | Accepted: 1 December 2021 | Published: 12 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Exosomes can be secreted from bone marrow mesenchymal stem cells (BMSCs) to extracellular space and exert anti-fibrotic effects, but the underlying mechanisms remain to be elucidated. Methods: 5/6 subtotal nephrotomy (SNx) rat models and TGF-β1-induced human renal proximal tubular epithelial cells (HRPTEpiCs) were established to simulate renal fibrosis. Renal function and fibrosis were assessed by Hematoxylin and Eeosin (HE) staining, Masson staining, immunohistochemistry, and western blot. The expression of Smad 7/Smurf 2 was detected in rats and HRPTEpiCs by western blot, and a further potential mechanism was explored using si-Smurf 2. Results: BMSC-Exo improved renal function, reduced the fibrotic region, down-regulated the expression of fibronectin, Collagen-I, α-SMA, and up-regulated E-cadherin in SNx models. In vitro study demonstrated that knocking down the expression of Smurf 2 significantly increased the expression of Smad 7, which could be enhanced by BMSC-Exo. BMSC-Exo could alleviate the fibrosis induced by TGF-β1 in tubular epithelial cells and enhanced the protective effect of si-Smurf 2 on renal fibrosis. Conclusions: BMSC-Exo inhibited renal fibrosis both in vivo and in vitro, partially, by regulating the Smurf 2/Smad 7 axis. BMSC-Exo enhanced the protective effect of si-Smurf 2 on fibrosis induced by transforming growth factor-β1 (TGF-β1).

Keywords
Renal fibrosis
Bone marrow mesenchymal stem cell
Exosome
Chronic kidney disease
Smurf 2/Smad 7
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