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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fengzhen Wang ◽  
Haihan Sun ◽  
Bangjie Zuo ◽  
Kun Shi ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
Early Stage ◽  
Tubulointerstitial Fibrosis ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Sprague Dawley ◽  
Mesenchymal Transition ◽  
Renal Tubulointerstitial Fibrosis ◽  
Renal Tubular

AbstractThis 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.

Inhibitory Effect of Gliquidone on Epithelial-to-Mesenchymal-Transition of Renal Tubular Epithelial Cells Under Diabetic Nephropathy Mouse Model

2022 ◽  
Vol 12 (1) ◽  
pp. 71-80
Author(s):  
Ting Liu ◽  
Jie Chen ◽  
Yiying Ying ◽  
Ling Shi ◽  
Zhengyue Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
Body Mass ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mesenchymal Transition ◽  
Renal Tubular

This research aimed to study the inhibitory effect of Glurenorm (gliquidone) on epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells based on the diabetic nephropathy (DN) model. In this study, 30 specific pathogen-free (SPF) mice were selected to construct DN model and randomly rolled into groups A, B, and C, with 10 mice in each group. Low-dose, mediumdose, and high-dose Glurenorm were administered intragastrically. The results showed that the serum urea nitrogen content (7.23±0.39 mmol/L, 6.18±0.46 mmol/L) of control and C group was considerably inferior to A group (8.01±0.48 mmol/L), and the content of C group was greatly lower than controls (P < 0.05). The creatinine clearance rate (2.97±0.44 mL/min, 4.02±0.31 mL/min) of mice in control and C group was notably superior to A group (2.18±0.38 mL/min), and that of C group was obviously higher versus controls (P < 0.05). After 5 weeks of intragastric intervention by Glurenorm, the body mass of the mice in control and C group was evidently lower relative to A group, and that of C group was obviously higher versus controls (P < 0.05). Mice in control and C group were remarkably lower in body mass at the 7th week after Glurenorm intervention versus A group, and C group was relatively lower versus controls (P < 0.05). In short, EMT played an important role in promoting the occurrence and progression of renal fibrosis. Glurenorm can reduce the progression of renal fibrosis, inhibit EMT of renal tubular epithelial cells, and effectively protect kidney function.

scholarly journals Metformin Attenuates Renal Tubulointerstitial Fibrosis via Upgrading Autophagy in the Early Stage of Diabetic Nephropathy

2021 ◽  
Author(s):  
Fengzhen Wang ◽  
Dong Sun ◽  
Haihan Sun ◽  
Bangjie Zuo ◽  
Kun Shi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial To Mesenchymal Transition ◽  
Early Stage ◽  
Renal Tissue ◽  
Tubulointerstitial Fibrosis ◽  
Sprague Dawley ◽  
Mesenchymal Transition ◽  
Renal Tubulointerstitial Fibrosis

Abstract The aim of the study was to compare the role of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluate its mechanism in high-glucose-treated Renal tubular epithelial cells (RTECs) in vitro. Sprague-Dawley (SD) rats were used to establish model of DN, then the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified via histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN was analyzed and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) was detected. Metformin markedly improved renal function and showed histological restoration of renal tissues especially in the early stage of DN, with a significant improvement of autophagy and a low expression of fibrotic biomarkers (Fibronectin and Collagen I) in renal tissue. RTECs under hyperglycemic conditions exhibited inactivation of p-AMPK and activation of EMT. But the promotion of AMPK activated by metformin significantly improved renal autophagic function, inhibited the EMT of RTECs, attenuated TIF, so as to effectively prevent or delay the course of DN. This evidence provided theoretical and experimental basis for the following research on the potential clinical usefulness of metformin for the treatment of diabetic TIF.

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