IDENTIFICATION OF POLYMORPHISMS WITHIN THE VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENE: CORRELATION WITH VARIATION IN VEGF PROTEIN PRODUCTION

Cytokine ◽  
2000 ◽  
Vol 12 (8) ◽  
pp. 1232-1235 ◽  
Author(s):  
Carolyn J Watson ◽  
Nicholas J.A Webb ◽  
Martyn J Bottomley ◽  
Paul E.C Brenchley
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Production ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Gene Correlation ◽  
Endothelial Growth Factor ◽  
Vegf Protein

scholarly journals Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor-β Pathway in Synovial Fibroblasts Derived from Osteoarthritis Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Shotaro Takano ◽  
Kentaro Uchida ◽  
Shintaro Shoji ◽  
Makoto Itakura ◽  
Dai Iwase ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Protein Production ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Vascular Endothelial ◽  
P38 Inhibitor ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Background. Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGFβ). However, the signaling pathway governing TGFβ-mediated regulation of VEGF in SFs has not been identified. Methods. OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGFβ (hrTGFβ), hrTGFβ + ALK5 inhibitor SB505124, hrTGFβ + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGFβ + p38 inhibitor SB203580 for 6 h. VEGF mRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting. Results. ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGFβ-induced VEGF mRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGFβ-mediated VEGF mRNA and VEGF protein production. Conclusion. TGFβ-mediated regulation of VEGF expression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway.

Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF165b) mRNA and protein

2004 ◽  
Vol 286 (4) ◽  
pp. F767-F773 ◽  
Author(s):  
Tai-Gen Cui ◽  
Rebecca R. Foster ◽  
Moin Saleem ◽  
Peter W. Mathieson ◽  
David A. Gillatt ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Concentration ◽  
Protein Production ◽  
No Reduction ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Despite production by podocytes of the proangiogenic molecule vascular endothelial growth factor-A (VEGF), the glomeruli are not sites of angiogenesis. We recently described mRNA expression of an inhibitory splice variant of VEGF (VEGF165b) in normal kidney (Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M, Shields JD, Peat D, Gillatt D, and Harper SJ. Cancer Res 62: 4123–4131, 2002). Available anti-VEGF antibodies do not distinguish stimulatory from inhibitory VEGF families. To assess the production of VEGF165 (stimulatory) and VEGF165b (inhibitory) isoforms by human podocytes, we examined both primary cultured and conditionally immortalized human podocytes using family- and isoform-specific RT-PCR. In addition, VEGF protein production was analyzed in podocytes, using isoform-specific double-strand small-interference RNAs (siRNA). RT-PCR demonstrated the production of VEGF189 mRNA by podocytes of both phenotypes. In contrast, on differentiation there was a splicing change from VEGF165 to VEGF165b mRNA. In addition, VEGF protein in the supernatant of conditionally immortalized, differentiated podocytes was reduced by VEGF165b siRNA to 20 ± 11% of the level of mock-transfected cells ( P < 0.01). No reduction was seen with mismatch siRNA. Moreover, there was no reduction in VEGF protein concentration in the supernatant of primary cultured, dedifferentiated human podocytes (109 ± 8% of mismatch siRNA, P > 0.1). In conclusion, differentiated but not dedifferentiated human podocytes secrete significant amounts of VEGF165b protein. It is possible that this may explain the paradox of high VEGF production in the glomerulus but no angiogenesis. Furthermore, the existence of this splicing switch in relation to podocyte phenotype suggests that alternative splicing of the VEGF pre-RNA is a regulated process that is open to manipulation and therefore could be a target for novel cancer therapies.

scholarly journals Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation

2008 ◽  
Vol 197 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Angélica Morales ◽  
Sumiko Morimoto ◽  
Lorenza Díaz ◽  
Guillermo Robles ◽  
Vicente Díaz-Sánchez
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pancreatic Tissue ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Rinm5f Cells ◽  
Vegf Gene ◽  
Rat Pancreas ◽  
Endothelial Growth Factor

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

scholarly journals Polymorphism in the regulatory regions –С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis

2017 ◽  
Vol 89 (5) ◽  
pp. 60-64 ◽  
Author(s):  
A V Shevchenko ◽  
V F Prokofyev ◽  
M A Korolev ◽  
N E Banshchikova ◽  
V I Konenkov
Keyword(s):  
Rheumatoid Arthritis ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Polymorphism Analysis ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Regulatory Regions ◽  
Female Patients ◽  
Healthy Women ◽  
Endothelial Growth Factor

Aim. To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. Results. There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. Conclusion. The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

Effects of Hypocrellin A on Expression of Vascular Endothelial Growth Factor and Endothelin-1 in Human Umbilical Endothelial Cells

2007 ◽  
Vol 35 (04) ◽  
pp. 713-723 ◽  
Author(s):  
Lei Dang ◽  
J. Paul Seale ◽  
Xianqin Qu
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Protein Expression ◽  
Vascular Endothelial ◽  
Naturally Occurring ◽  
Hypocrellin A ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Increased endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC) are co-contributors to endothelial hyperpermeability in diabetes. Several lines of evidence have suggested a hypothesis that activation of specific PKC isoforms are the causative factor in ET-1 and VEGF mediated endothelial dysfunction. In the present study, we tested this hypothesis with hypocrellin A, a naturally occurring PKC inhibitor from a Chinese plant. Human umbilical vein endothelial cells (HUVECs) were incubated with 20 mM glucose in both the presence and absence of hypocrellin A, after which, the protein expression and release of VEGF and mRNA expression and release of ET-1 were measured. VEGF and ET-1 were released into the medium and expressions of VEGF protein and ET-1 mRNA were significantly increased in HUVECs incubated with 20 mM glucose. Hypocrellin A (150 nM) significantly decreased VEGF release (117 ± 3 vs. 180 ± 11 pg/mg, p < 0.05) and VEGF protein expression (from 130 ± 14% to 88 ± 18.5%, p < 0.05). ET-1 release was also reduced in hypocrellin A treated HUVECs (63.3 ± 9.9 vs. 75.2 ± 12.6 ng/mg). Hypocrellin A significantly reversed the effect of high glucose on ET-1 mRNA expression ( p < 0.05). The results revealed that PKC activation plays a pivotal role in VEGF and ET-1 mediated endothelial permeability. The naturally occurring compound hypocrellin A may be a potentially novel treatment for endothelial dysfunction in diabetes.

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