Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir

Juan Jin,* Fengmei Qian,* Danna Zheng, Wenfang He, Jianguang Gong, Qiang He Department of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors c...

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Autores principales:	Jin J, Qian F, Zheng D, He W, Gong J, He Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	chronic kidney disease renal fibrosis mesenchymal stem cells exosomes and micrornas Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6d65559914da4f7e87952a98ff1a3c8d
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spelling	oai:doaj.org-article:6d65559914da4f7e87952a98ff1a3c8d2021-12-02T15:01:49ZMesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir1178-2013https://doaj.org/article/6d65559914da4f7e87952a98ff1a3c8d2021-05-01T00:00:00Zhttps://www.dovepress.com/mesenchymal-stem-cells-attenuate-renal-fibrosis-via-exosomes-mediated--peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Juan Jin,* Fengmei Qian,* Danna Zheng, Wenfang He, Jianguang Gong, Qiang He Department of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguang Gong; Qiang HeDepartment of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, 158 Shangtang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaEmail gojigu311@163.com; qianghe1973@126.comBackground: Renal fibrosis is a chronic and progressive process affecting kidneys in chronic kidney disease (CKD). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to alleviate renal fibrosis and injury, but the mechanism of MSCs-Exo-induced renal protection remains unknown.Methods: In this study, MSCs were transfected with let-7i-5p antagomir (anti-let-7i-5p), and then exosomes were isolated from the transfected MSCs to deliver anti-let-7i-5p oligonucleotides to inhibit the level of let-7i-5p in kidney tubular epithelial cells (NRK-52E).Results: In both NRK-52E cells stimulated by TGF-β 1 and the mouse kidneys after unilateral ureteral obstruction (UUO), we demonstrated increased level of let-7i-5p. In addition, MSCs-Exo can deliver anti-let-7i-5p to reduce the level of let-7i-5p in NRK-52E cells and increase the expression of its target gene TSC1. Moreover, exosomal anti-let-7i-5p reduced extracellular matrix (ECM) deposition and attenuated epithelial–mesenchymal transition (EMT) process in transforming growth factor beta 1 (TGF-β 1)-stimulated NRK-52E cells and in the kidneys of UUO-treated mice. Meanwhile, mice received exosomal anti-let-7i-5p displayed reduced renal fibrosis and improved kidney function when challenged with UUO. Furthermore, exosomal anti-let-7i-5p promoted the activation the tuberous sclerosis complex subunit 1/mammalian target of rapamycin (TSC1/mTOR) signaling pathway in vivo and in vitro.Conclusion: In conclusion, exosomal anti-let-7i-5p from MSCs exerts anti-fibrotic effects in TGF-β 1-induced fibrogenic responses in NRK52E cells in vitro as well as in UUO-induced renal fibrosis model in vivo. These results provided a novel perspective on improving renal fibrosis by MSCs-Exo.Keywords: chronic kidney disease, renal fibrosis, mesenchymal stem cells, exosomes and microRNAsJin JQian FZheng DHe WGong JHe QDove Medical Pressarticlechronic kidney diseaserenal fibrosismesenchymal stem cellsexosomes and micrornasMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 3565-3578 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic kidney disease renal fibrosis mesenchymal stem cells exosomes and micrornas Medicine (General) R5-920
spellingShingle	chronic kidney disease renal fibrosis mesenchymal stem cells exosomes and micrornas Medicine (General) R5-920 Jin J Qian F Zheng D He W Gong J He Q Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
description	Juan Jin,* Fengmei Qian,* Danna Zheng, Wenfang He, Jianguang Gong, Qiang He Department of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguang Gong; Qiang HeDepartment of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, 158 Shangtang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaEmail gojigu311@163.com; qianghe1973@126.comBackground: Renal fibrosis is a chronic and progressive process affecting kidneys in chronic kidney disease (CKD). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to alleviate renal fibrosis and injury, but the mechanism of MSCs-Exo-induced renal protection remains unknown.Methods: In this study, MSCs were transfected with let-7i-5p antagomir (anti-let-7i-5p), and then exosomes were isolated from the transfected MSCs to deliver anti-let-7i-5p oligonucleotides to inhibit the level of let-7i-5p in kidney tubular epithelial cells (NRK-52E).Results: In both NRK-52E cells stimulated by TGF-β 1 and the mouse kidneys after unilateral ureteral obstruction (UUO), we demonstrated increased level of let-7i-5p. In addition, MSCs-Exo can deliver anti-let-7i-5p to reduce the level of let-7i-5p in NRK-52E cells and increase the expression of its target gene TSC1. Moreover, exosomal anti-let-7i-5p reduced extracellular matrix (ECM) deposition and attenuated epithelial–mesenchymal transition (EMT) process in transforming growth factor beta 1 (TGF-β 1)-stimulated NRK-52E cells and in the kidneys of UUO-treated mice. Meanwhile, mice received exosomal anti-let-7i-5p displayed reduced renal fibrosis and improved kidney function when challenged with UUO. Furthermore, exosomal anti-let-7i-5p promoted the activation the tuberous sclerosis complex subunit 1/mammalian target of rapamycin (TSC1/mTOR) signaling pathway in vivo and in vitro.Conclusion: In conclusion, exosomal anti-let-7i-5p from MSCs exerts anti-fibrotic effects in TGF-β 1-induced fibrogenic responses in NRK52E cells in vitro as well as in UUO-induced renal fibrosis model in vivo. These results provided a novel perspective on improving renal fibrosis by MSCs-Exo.Keywords: chronic kidney disease, renal fibrosis, mesenchymal stem cells, exosomes and microRNAs
format	article
author	Jin J Qian F Zheng D He W Gong J He Q
author_facet	Jin J Qian F Zheng D He W Gong J He Q
author_sort	Jin J
title	Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
title_short	Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
title_full	Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
title_fullStr	Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
title_full_unstemmed	Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir
title_sort	mesenchymal stem cells attenuate renal fibrosis via exosomes-mediated delivery of microrna let-7i-5p antagomir
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/6d65559914da4f7e87952a98ff1a3c8d
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Mesenchymal Stem Cells Attenuate Renal Fibrosis via Exosomes-Mediated Delivery of microRNA Let-7i-5p Antagomir

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