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

نویسندگان

  • Catharine Whiteside
  • Hong Wang
  • Ling Xia
  • Snezana Munk
  • Howard J. Goldberg
  • I. George Fantus
چکیده

Peroxisome proliferator-activated receptor (PPARgamma), a ligand-dependent transcription factor, negatively modulates high glucose effects. We postulated that rosiglitazone (RSG), an activator of PPARgamma prevents 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, PPARgamma mRNA and protein were reduced within 3 h, and enhanced ROS generation, expression of p22(phox), VEGF and collagen IV, and PKC-zeta membrane association were prevented by RSG. In NG, inhibition of PPARgamma caused 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, PPARgamma is a negative modulator of HG-induced signaling that acts through PKC-zeta but not AMPK and regulates VEGF and collagen IV expression by mesangial cells.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Expression of vascular endothelial growth factor in response to high glucose in rat mesangial cells.

Diabetic nephropathy associated with hyperglycemia is characterized by glomerular hyperfiltration and endothelial dysfunction. Vascular endothelial growth factor (VEGF) is known to be primarily involved in neoangiogenesis and increased endothelial permeability. The purpose of this study was to investigate VEGF expression in response to high glucose in rat cultured mesangial cells and to identif...

متن کامل

Inhibition of Src Kinase Blocks High Glucose–Induced EGFR Transactivation and Collagen Synthesis in Mesangial Cells and Prevents Diabetic Nephropathy in Mice

Chronic exposure to high glucose leads to diabetic nephropathy characterized by increased mesangial matrix protein (e.g., collagen) accumulation. Altered cell signaling and gene expression accompanied by oxidative stress have been documented. The contribution of the tyrosine kinase, c-Src (Src), which is sensitive to oxidative stress, was examined. Cultured rat mesangial cells were exposed to h...

متن کامل

Translational Physiology Glibenclamide prevents increased extracellular matrix formation induced by high glucose concentration in mesangial cells

Giannico G, Cortes P, Baccora MH, Hassett C, Taube DW, Yee J. Glibenclamide prevents increased extracellular matrix formation induced by high glucose concentration in mesangial cells. Am J Physiol Renal Physiol 292: F57–F65, 2007. First published August 8, 2006; doi:10.1152/ajprenal.00210.2006.—Other than stimulation of cell contractility, little is known about the potential metabolic effects i...

متن کامل

Reactive oxygen species, PKC- 1, and PKC- mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells

Xia L, Wang H, Munk S, Frecker H, Goldberg HJ, Fantus IG, Whiteside CI. Reactive oxygen species, PKC1, and PKCmediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells. Am J Physiol Endocrinol Metab 293: E1280–E1288, 2007. First published August 21, 2007; doi:10.1152/ajpendo.00223.2007.—Vascular endothelial growth factor (VEGF) is implicated in the developmen...

متن کامل

Patterns of Vascular Endothelial Growth Factor Expression in Hematopoietic Malignant Cells

Background and Objective: Vascular endothelial growth factor (VEGF) is a cytokine which is overexpressed in many malignant cancers including leukemia. VEGF plays an important role in tumor invasion and metastasis. Determination of the pattern of VEGF expression in human leukemic cell lines could be useful not only in screening of new antileukemic agents but also to study the mechanism of their ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 2009  شماره 

صفحات  -

تاریخ انتشار 2009