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

2000 ◽  
Vol 165 (3) ◽  
pp. 617-624 ◽  
Author(s):  
NH Kim ◽  
HH Jung ◽  
DR Cha ◽  
DS Choi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Protein Levels ◽  
Calphostin C ◽  
Endothelial Growth Factor

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 identify its signal pathway via protein kinase C (PKC). Rat mesangial cells were cultured with different concentrations of glucose: normal (5 mM d-glucose), medium (15 mM d-glucose) and high (30 mm d-glucose). Calphostin-C as a PKC inhibitor and phorbol myristate acetate (PMA) as a PKC downregulator were instillated into culture media to evaluate the role of PKC in mediating the glucose-induced increase in VEGF expression. High glucose increased expression of VEGF at the mRNA and protein levels, identified by semi-quantitative RT-PCR and western blotting, within 3 h and in a time- and glucose concentration-dependent manner. Calphostin-C and PMA inhibited glucose-induced increases in VEGF expression at the mRNA and protein levels. In conclusion, high glucose can directly increase VEGF expression in rat mesangial cells via a PKC-dependent mechanism. These results suggest that VEGF could be a potential mediator of glomerular hyperfiltration and proteinuria in diabetic nephropathy.

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

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Catharine Whiteside ◽  
Hong Wang ◽  
Ling Xia ◽  
Snezana Munk ◽  
Howard J. Goldberg ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Collagen Iv ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

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.

Reactive oxygen species, PKC-β1, and PKC-ζ mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells

2007 ◽  
Vol 293 (5) ◽  
pp. E1280-E1288 ◽  
Author(s):  
Ling Xia ◽  
Hong Wang ◽  
Snezana Munk ◽  
Helena Frecker ◽  
Howard J. Goldberg ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Endothelial Growth Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Vegf Expression ◽  
Pkc Β ◽  
Pkc Ζ ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is implicated in the development of proteinuria in diabetic nephropathy. High ambient glucose present in diabetes stimulates VEGF expression in several cell types, but the molecular mechanisms are incompletely understood. Here primary cultured rat mesangial cells served as a model to investigate the signal transduction pathways involved in high-glucose-induced VEGF expression. Exposure to high glucose (25 mM) significantly increased VEGF mRNA evaluated by real-time PCR by 3 h, VEGF cellular protein content assessed by immunoblotting or immunofluorescence within 24 h, and VEGF secretion by 24 h. High-glucose-induced VEGF expression was blocked by an antioxidant, Tempol, and antisense oligonucleotides directed against p22phox, a NADPH oxidase subunit. Inhibition of protein kinase C (PKC)-β1 with the specific pharmacological inhibitor LY-333531 or inhibition of PKC-ζ with a cell permeable specific pseudosubstrate peptide also prevented enhanced VEGF expression in high glucose. Enhanced VEGF secretion in high glucose was prevented by Tempol, PKC-β1, or PKC-ζ inhibition. In normal glucose (5.6 mM), overexpression of p22phox or constitutively active PKC-ζ enhanced VEGF expression. Hypoxia inducible factor-1α protein was significantly increased in high glucose only by 24 h, suggesting a possible contribution to high-glucose-stimulated VEGF expression at later time points. Thus reactive oxygen species generated by NADPH oxidase, and both PKC-β1 and -ζ, play important roles in high-glucose-stimulated VEGF expression and secretion by mesangial cells.

scholarly journals Differential regulation of vascular endothelial growth factor and its receptor fms-like-tyrosine kinase is mediated by nitric oxide in rat renal mesangial cells

1999 ◽  
Vol 338 (2) ◽  
pp. 367-374 ◽  
Author(s):  
Stefan FRANK ◽  
Birgit STALLMEYER ◽  
Heiko KÄMPFER ◽  
Christian SCHAFFNER ◽  
Josef PFEILSCHIFTER
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Mesangial Cells ◽  
Differential Regulation ◽  
Moderate Increase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

Under conditions associated with local and systemic inflammation, mesangial cells and invading immune cells are likely to be responsible for the release of large amounts of nitric oxide (NO) in the glomerulus. To further define the mechanisms of NO action in the glomerulus, we attempted to identify genes which are regulated by NO in rat glomerular mesangial cells. We identified vascular endothelial growth factor (VEGF) and its receptor fms-like tyrosine kinase (FLT-1) to be under the regulatory control of exogenously applied NO in these cells. Using S-nitroso-glutathione (GSNO) as an NO-donating agent, VEGF expression was strongly induced, whereas expression of its FLT-1 receptor simultaneously decreased. Expressional regulation of VEGF and FLT-1 mRNA was transient and occurred rapidly within 1–3 h after GSNO treatment. Expression of a second VEGF-specific receptor, fetal liver kinase-1 (FLK-1/KDR), could not be detected. The inflammatory cytokine interleukin-1β mediated a moderate increase in VEGF expression after 24 h and had no influence on FLT-1 expression. In contrast, platelet-derived growth factor–BB and basic fibroblast growth factor had no effect on VEGF expression, but strongly induced FLT-1 mRNA levels. Obviously, there is a differential regulation of VEGF and its receptor FLT-1 by NO, cytokines and growth factors in rat mesangial cells.

Vascular Endothelial Growth Factor (VEGF) Expression in Healthy and Inflamed Human Dental Pulps

2002 ◽  
Vol 28 (1) ◽  
pp. 20-23 ◽  
Author(s):  
L ARTESE ◽  
C RUBINI ◽  
G FERRERO ◽  
M FIORONI ◽  
A SANTINELLI ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

scholarly journals Vascular Endothelial Growth Factor (VEGF) Expression in Human Coronary Atherosclerotic Lesions

Circulation ◽  
1998 ◽  
Vol 98 (20) ◽  
pp. 2108-2116 ◽  
Author(s):  
Mayumi Inoue ◽  
Hiroshi Itoh ◽  
Makiko Ueda ◽  
Takahiko Naruko ◽  
Akiko Kojima ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Atherosclerotic Lesions ◽  
Endothelial Growth Factor

scholarly journals The Involvement of Angiotensin Type 1 and Type 2 Receptors in Estrogen-Induced Cell Proliferation and Vascular Endothelial Growth Factor Expression in the Rat Anterior Pituitary

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hanna Lawnicka ◽  
Dorota Ptasinska-Wnuk ◽  
Slawomir Mucha ◽  
Jolanta Kunert-Radek ◽  
Marek Pawlikowski ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Blood Vessels ◽  
Proliferation Index ◽  
Pituitary Cells ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Rat Pituitary ◽  
Endothelial Growth Factor

The aim of our study was to examine the involvement of renin-angiotensin system (RAS) in estrogen-induced lactotropes proliferation and vascular endothelial growth factor (VEGF) expression in rat pituitary. The study was performed on Fisher 344 rats underwent 8-day treatment with diethylstilboestrol (DES). The proliferation index (PCNA) and VEGF expression in pituitary sections were estimated using immunohistochemical methods. Treatment with DES increased the number of PCNA-positive cells, VEGF-positive cells, and VEGF-positive blood vessels in pituitary. Stimulatory effect of estrogen on cell proliferation and VEGF expression in blood vessels was attenuated by losartan, PD123319, and captopril. VEGF immunoreactivity in pituitary cells of DES-treated rats was decreased by AT1 antagonist and not changed by AT2 blocker and ACE inhibitor. Our findings suggest the involvement of RAS in DES-induced cell proliferation and VEGF expression in pituitary. Both the AT1 and AT2 receptors appear to mediate the estrogen-dependent mitogenic and proangiogenic effects in rat pituitary.

scholarly journals Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia

2009 ◽  
Vol 137 (7-8) ◽  
pp. 379-383 ◽  
Author(s):  
Ana Vidovic ◽  
Gradimir Jankovic ◽  
Dragica Tomin ◽  
Maja Perunicic-Jovanovic ◽  
Irena Djunic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor ◽  
The Impact

Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

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