scholarly journals Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) in alveolar epithelial cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hengning Ke ◽  
Katarzyna Chmielarska Masoumi ◽  
Kristofer Ahlqvist ◽  
Michael J. Seckl ◽  
Kristina Rydell-Törmänen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Vascular Endothelial ◽  
Alveolar Epithelial ◽  
Endothelial Growth Factor

scholarly journals Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
James P. Maloney ◽  
Li Gao
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Proinflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Vascular Endothelial ◽  
Lung Epithelium ◽  
Vegf Expression ◽  
Alveolar Epithelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is an endothelial permeability mediator that is highly expressed in lung epithelium. In nonlung cells proinflammatory cytokines have been shown to increase VEGF expression, but their effects on lung epithelium remain unclear. We hypothesized that increases in alveolar epithelial cell VEGF RNA and protein expression occur after exposure to proinflammatory cytokines. We tested this using human alveolar epithelial cells (A549) stimulated with 5 proinflammatory cytokines. VEGF RNA expression was increased 1.4–2.7-fold in response to IL-1, IL-6, IL-8, TNF-α, or TGF-βover 6 hours, with TGF-βhaving the largest response. TNF-αincreased VEGF RNA as early as 1 hour. A mix of IL-1, IL-6, and IL-8 had effects similar to IL-1. TNF-αincreased protein expression as early as 4 hours and had a sustained effect at 16 hours, whereas IL-1 did not increase protein expression. Only VEGF165was present in cultured A549 cells, yet other isoforms were seen in human lung tissue. Increased expression of VEGF in alveolar epithelial cells occurs in response to proinflammatory cytokines. Increased VEGF expression likely contributes to the pathogenesis of inflammatory lung diseases and to the angiogenic phenotype of lung cancer, a disease typically preceded by chronic inflammation.

scholarly journals The type 2 vascular endothelial growth factor receptor recruits insulin receptor substrate-1 in its signalling pathway

2002 ◽  
Vol 368 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Duraisamy SENTHIL ◽  
Goutam GHOSH CHOUDHURY ◽  
Basant K. BHANDARI ◽  
Balakuntalam S. KASINATH
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Kinase Activity ◽  
Insulin Receptor Substrate ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) isoforms exert their biological effects through receptors that possess intrinsic tyrosine kinase activity. Whether VEGF binding to its receptors recruits insulin receptor substrate (IRS) family of docking proteins to the receptor is not known. Following incubation of mouse kidney proximal tubular epithelial cells with VEGF, we observed an increase in tyrosine phosphorylation of several proteins, including one of 200kDa, suggesting possible regulation of phosphorylation of IRS proteins. VEGF augmented tyrosine phosphorylation of IRS-1 in kidney epithelial cells and rat heart endothelial cells in a time-dependent manner. In the epithelial cells, association of IRS-1 with type 2 VEGF receptor was promoted by VEGF. VEGF also increased association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase), and PI 3-kinase activity in IRS-1 immunoprecipitates was increased in VEGF-treated cells. Incubation of epithelial cells with antisense IRS-1 oligonucleotide, but not sense oligonucleotide, reduced expression of the protein and VEGF-induced PI 3-kinase activity in IRS-1 immunoprecipitates. Additionally, VEGF-induced protein synthesis was also impaired by antisense but not sense IRS-1 oligonucleotide. These data provide the first evidence that binding of VEGF to its type 2 receptor promotes association of IRS-1 with the receptor complex. This association may account for some of the increase in VEGF-induced PI 3-kinase activity, and the increase in de novo protein synthesis seen in renal epithelial cells.

Long-Term Follow-Up of Immunocytochemical Analysis of Vascular Endothelial Growth Factor (VEGF), and Its Two Receptors, VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR), in Oesophagogastric Cancer

2013 ◽  
Vol 28 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Ronan T. Gray ◽  
Mark E. O'Donnell ◽  
Perry Maxwell ◽  
James A. McGuigan ◽  
Gary M. Spence
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Lymphovascular Invasion ◽  
Prognostic Significance ◽  
Vascular Endothelial ◽  
Immunocytochemical Analysis ◽  
Endothelial Growth Factor ◽  
Oesophagogastric Cancer

Background The prognostic significance of immunocytochemical analysis of tumour vascular endothelial growth factor (VEGF) and its 2 receptors, VEGF-R1 and VEGF-R2, remains incompletely investigated in patients with oesophagogastric cancer. Methods Patients undergoing surgical resection were prospectively recruited between February 1999 and August 2000. Immunocytochemical analysis of VEGF, VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR) was undertaken using validated techniques. Patients were followed up over a 10-year period using the Northern Ireland Cancer Registry. Results Sixty-one patients were recruited (male=45, 73.8%) with a median age of 66.0 years (range 39-83). Forty-seven (77.0%) adenocarcinomas and 14 (23.0%) squamous cell carcinomas were resected. UICC tumour staging was: stage I=14.7%, II=24.6%, III=54.1% and IV=6.6%. VEGF, VEGF-R1 and VEGF-R2 were over-expressed in tumour epithelial cells. VEGF-R2 expression was decreased in the presence of lymphovascular invasion and higher tumour grade. The 10-year survival rate was 19.7% (n=12) with a median follow-up of 808 (IQR 356-2313) days. On univariate analysis only lymphovascular invasion significantly predicted poor prognosis in this cohort (p=0.05). Conclusion VEGF, VEGF-R1 and VEGF-R2 were over-expressed in tumour epithelial cells. VEGF-R2 expression was decreased in the presence of more aggressive pathological variables. Larger studies are required to assess the prognostic significance of these biomarkers in oesophagogastric cancer.

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