Metformin suppresses LRG1 and TGFβ1/ALK1-induced angiogenesis and protects against ultrastructural changes in rat diabetic nephropathy - 13/01/23
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Abstract |
Diabetic nephropathy (DN) has high prevalence and poor prognosis which make it a research priority for scientists. Since metformin, a hypoglycaemic drug, has been found to prolong the survival of mice with DN. This study aims at investigating the molecular mechanisms leading to DN in rats and to explore the role of leucine-rich α-2-glycoprotein-1 (LRG1), activin-like kinase1 (ALK1), and transforming growth factor–β (TGFβ1) in the pathologic alterations seen in DN. The aim was also extended to explore the protective action of metformin against DN in rats and its influence on LRG1and ALK1/TGFβ1 induced renal angiogenesis. 24 male rats were used. Rats were assigned as, the vehicle group, the diabetic control group and diabetic + metformin (100 and 200 mg/kg) groups. Kidney samples were processed for histopathology, immunohistochemistry and biochemical analysis. Bioinformatic analysis of studied proteins was done to determine protein-protein interactions. Metformin reduced serum urea and creatinine significantly, decreased the inflammatory cytokine levels and reduced LRG1, TGFβ1, ALK1 and vascular endothelial growth factor (VEGF) proteins in rat kidneys. Bioinformatic analysis revealed interactions between the studied proteins. Metformin alleviated the histopathological changes observed in the diabetic rats such as the glomerular surface area and increased Bowman’s space diameter. Metformin groups showed decreased VEGF immunostaining compared to diabetic group. Metformin shows promising renoprotective effects in diabetic model that was at least partly mediated by downregulation of LRG1 and TGFβ1/ALK1-induced renal angiogenesis. These results further explain the molecular mechanism of metformin in DN management.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | STZ induced features of functional and histological diabetic nephropathy in rats. |
• | Metformin alleviated the pathological features and renal fibrosis in nephropathy. |
• | Metformin suppresses LRG1 and TGFβ1/ALK1-induced renal angiogenesis. |
• | Metformin protects against ultrastructural changes in rat diabetic nephropathy. |
Keywords : ALK1, Diabetic nephropathy, Metformin, LRG1, Rat, TGFβ1-induced angiogenesis
Plan
Vol 158
Article 114128- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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