scholarly journals Distribution of vascular endothelial growth factor (VEGF) and its binding sites at the maternal-fetal interface during gestation in pigs

Reproduction ◽  
2001 ◽  
pp. 753-760 ◽  
Author(s):  
DS Charnock-Jones ◽  
DE Clark ◽  
D Licence ◽  
K Day ◽  
FB Wooding ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Vascular Endothelial ◽  
Epithelial Layers ◽  
Endothelial Growth Factor ◽  
Maternal Fetal Interface

Pigs show epitheliochorial placentation, in which the maternal uterine epithelium and the fetal trophectoderm become closely apposed. There is no invasion of trophoblast into the maternal tissue, and nutrient and waste exchange take place across two epithelial layers beneath which a complex network of capillaries forms. Later in gestation, the epithelial cells become indented by blood vessels, which greatly reduces the distance for diffusion between the two circulatory systems. Vascular endothelial growth factor is a secreted homodimeric angiogenic growth factor that is involved in physiological and pathological angiogenesis. Its receptors are generally restricted to endothelial cells. Ligand binding, in situ hybridization and immunohistochemistry were carried out in pig placenta throughout gestation to investigate the possible role of vascular endothelial growth factor and its receptors in non-invasive placentation. In situ hybridization and immunohistochemistry revealed that mRNA and immunoreactivity for vascular endothelial growth factor were localized in both maternal and fetal epithelial cells at the maternal-fetal interface and over the maternal glands, although the signal was generally weaker in the maternal glands. Ligand binding was used to localize for vascular endothelial growth factor receptors; no binding was observed over the maternal glands, but very strong binding was localized to the endometrial blood vessels. At the interface between maternal and fetal tissue, a similar pattern was observed whereby the numerous small capillaries at the bases of the two apposed epithelia bound vascular endothelial growth factor specifically. It is concluded that vascular endothelial growth factor produced by the maternal and fetal epithelial layers promotes the growth of capillaries locally, which would facilitate the development of two vascular networks for the efficient transfer of nutrients and waste products.

scholarly journals Vascular Permeability Factor/Vascular Endothelial Growth Factor and Vascular Stroma Formation in Neoplasia: Insights from In Situ Hybridization Studies

1998 ◽  
Vol 46 (5) ◽  
pp. 569-575 ◽  
Author(s):  
Lawrence F. Brown ◽  
Anthony J. Guidi ◽  
Kathi Tognazzi ◽  
Harold F. Dvorak
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Permeability Factor ◽  
Endothelial Growth Factor ◽  
Vascular Stroma

The formation of vascular stroma plays an important role in the pathophysiology of malignancy. We describe the use of in situ hybridization in our laboratory as a tool to study the role of vascular permeability factor/vascular endothelial growth factor in the angiogenesis associated with malignancy.

Expression of vascular endothelial growth factor and its receptor Flk-1 in human neuroblastoma using in situ hybridization

2002 ◽  
Vol 37 (12) ◽  
pp. 1747-1750 ◽  
Author(s):  
Masahiro Fukuzawa ◽  
Hiroaki Sugiura ◽  
Tsugumichi Koshinaga ◽  
Taro Ikeda ◽  
Noritugu Hagiwara ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Human Neuroblastoma ◽  
Endothelial Growth Factor

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.

Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues

1993 ◽  
Vol 264 (4) ◽  
pp. C995-C1002 ◽  
Author(s):  
W. T. Monacci ◽  
M. J. Merrill ◽  
E. H. Oldfield
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Rat Tissues ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Organ Specific ◽  
Normal Rat ◽  
Endothelial Growth Factor ◽  
The Brain

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.

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