Resveratrol attenuates diabetic nephropathy via modulating angiogenesis

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Diabetic nephropathy (DN) pathogenesis involves aberrant angiogenesis.
• Resveratrol is a polyphenol with known antiangiogenic properties.
• Investigating resveratrol's therapeutic effects on DN is crucial.

Purpose of the Study:

• To investigate the therapeutic potential of resveratrol in a type 1 diabetic rat model.
• To elucidate the mechanisms underlying resveratrol's effects on angiogenesis in DN.
• To examine resveratrol's impact on angiogenic factors and cellular pathways in diabetic kidneys and cells.

Main Methods:

• Established a type 1 diabetic rat model and treated with resveratrol.
• Assessed kidney function markers (urine albumin excretion, creatinine clearance, kidney weight).
• Analyzed histological changes (glomerular diameter, mesangium, GBM thickness, fibrosis) and expression of angiogenic factors (VEGF, Flk-1, angiopoietins, Tie-2) via molecular techniques. Evaluated effects on cultured podocytes and endothelial cells under high glucose conditions, including Sirt1 modulation and endothelial permeability assays.

Main Results:

• Resveratrol treatment significantly reduced albuminuria, kidney weight, and improved creatinine clearance in diabetic rats.
• Histological analysis revealed resveratrol mitigated glomerular hypertrophy, mesangial expansion, GBM thickening, and renal fibrosis.
• Resveratrol normalized the expression of VEGF, Flk-1, and angiopoietin 2, while restoring Tie-2 levels in diabetic kidneys. It also downregulated high glucose-induced VEGF and Flk-1 in cultured cells, an effect dependent on Sirt1.
• Resveratrol inhibited VEGF-induced endothelial hyperpermeability and junction disruption.

Conclusions:

• Resveratrol demonstrates significant renoprotective effects in a type 1 DN model.
• The therapeutic action of resveratrol in DN is mediated through the modulation of angiogenesis, involving key factors like VEGF and Sirt1.
• Resveratrol holds promise as a therapeutic agent for managing diabetic nephropathy by targeting aberrant angiogenesis.