Rosiglitazone Reduces Angiotensin II and Advanced Glycation End Product-dependent Sustained Nuclear Factor-κB Activation in Cultured Human Proximal Tubular Epithelial Cells

Tubular damage is a major feature in the development of diabetic nephropathy. This study investigates the effects of the thiazolidindione rosiglitazone on angiotensin II and advanced glycation end product-induced tubular activation in human proximal tubular epithelial cells in vitro. Angiotensin II and advanced glycation end products, both induced a dose-dependent sustained activation of the redox-sensitive transcription factor, Nuclear Factor kappa B (NF-kappa B). Nuclear translocation of NF-kappa B was evident already after one hour and persistent for more than four days. Co-incubation of proximal tubular epithelial cells with rosiglitazone significantly reduced angiotensin II and advanced glycation end product-mediated generation of reactive oxygen species, angiotensin II-dependent advanced glycation end product formation, NF-kappa B activation, and NF-kappa B-dependent pro inflammatory gene expression. Most importantly, rosiglitazone effects on NF kappa B activation were maximal at later time points, indicating that rosiglitazone treatment confers long lasting renoprotective effects.