Rosiglitazone Prevents High Glucose-Induced Vascular Endothelial Growth Factor and Collagen IV Expression in Cultured Mesangial Cells

[摘要] Peroxisome proliferator-activated receptor (PPARγ), a ligand-dependent transcription factor, negatively modulates high glucose effects. We postulated that rosiglitazone (RSG), an activator of PPARγprevents the upregulation of vascular endothelial growth factor (VEGF) and collagen IV by mesangial cells exposed to high glucose. Primary cultured rat mesangial cells were growth-arrested in 5.6 mM (NG) or 25 mM D-glucose (HG) for up to 48 hours. In HG, PPARγmRNA and protein were reduced within 3 h, and enhanced ROS generation, expression ofp22phox, VEGF and collagen IV, and PKC-ζmembrane association were prevented by RSG. In NG, inhibition of PPARγcaused ROS generation and VEGF expression that were unchanged by RSG. Reduced AMP-activated protein kinase (AMPK) phosphorylation in HG was unchanged with RSG, and VEGF expression was unaffected by AMPK inhibition. Hence, PPARγis a negative modulator of HG-induced signaling that acts through PKC-ζbut not AMPK and regulates VEGF and collagen IV expression by mesangial cells.

[学科分类] 内分泌与代谢学