Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy

Abstract This study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used...

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Autores principales:	Fengzhen Wang, Haihan Sun, Bangjie Zuo, Kun Shi, Xin Zhang, Chi Zhang, Dong Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/980d13f8a4db494c920b14ce6fcb5e50
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spelling	oai:doaj.org-article:980d13f8a4db494c920b14ce6fcb5e502021-12-02T16:27:54ZMetformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy10.1038/s41598-021-95827-52045-2322https://doaj.org/article/980d13f8a4db494c920b14ce6fcb5e502021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95827-5https://doaj.org/toc/2045-2322Abstract This study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used to establish a model of DN, and the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified using histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN, and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) were investigated. Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue. Under hyperglycemic conditions, renal tubular epithelial cells inactivated p-AMPK and activated partial EMT. Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN. This evidence provides theoretical and experimental basis for the following research on the potential clinical application of metformin in the treatment of diabetic TIF.Fengzhen WangHaihan SunBangjie ZuoKun ShiXin ZhangChi ZhangDong SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fengzhen Wang Haihan Sun Bangjie Zuo Kun Shi Xin Zhang Chi Zhang Dong Sun Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
description	Abstract This study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used to establish a model of DN, and the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified using histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN, and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) were investigated. Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue. Under hyperglycemic conditions, renal tubular epithelial cells inactivated p-AMPK and activated partial EMT. Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN. This evidence provides theoretical and experimental basis for the following research on the potential clinical application of metformin in the treatment of diabetic TIF.
format	article
author	Fengzhen Wang Haihan Sun Bangjie Zuo Kun Shi Xin Zhang Chi Zhang Dong Sun
author_facet	Fengzhen Wang Haihan Sun Bangjie Zuo Kun Shi Xin Zhang Chi Zhang Dong Sun
author_sort	Fengzhen Wang
title	Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
title_short	Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
title_full	Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
title_fullStr	Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
title_full_unstemmed	Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
title_sort	metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/980d13f8a4db494c920b14ce6fcb5e50
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Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy

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