scholarly journals Increased Pituitary Vascular Endothelial Growth Factor-A in Dopaminergic D2 Receptor Knockout Female Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2952-2962 ◽  
Author(s):  
C. Cristina ◽  
G. Díaz-Torga ◽  
A. Baldi ◽  
A. Góngora ◽  
M. Rubinstein ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
D2 Receptor ◽  
Prolactin Secretion ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Vegf Expression ◽  
Female Mice ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF)-A is an important angiogenic cytokine in cancer and pathological angiogenesis and has been related to the antiangiogenic activity of dopamine in endothelial cells. We investigated VEGF expression, localization, and function in pituitary hyperplasia of dopamine D2 receptor (D2R)-knockout female mice. Pituitaries from knockout mice showed increased protein and mRNA VEGF-A expression when compared with wild-type mice. In wild-type mice, prolonged treatment with the D2R antagonist, haloperidol, enhanced pituitary VEGF expression and prolactin release, suggesting that dopamine inhibits pituitary VEGF expression. VEGF expression was also increased in pituitary cells from knockout mice, even though these cells proliferated less in vitro when compared with wild-type cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay, proliferating cell nuclear antigen expression, and [3H]thymidine incorporation. In contrast to other animal models, estrogen did not increase pituitary VEGF protein and mRNA expression and lowered serum prolactin secretion in vivo and in vitro in both genotypes. VEGF (10 and 30 ng/ml) did not modify pituitary cell proliferation in either genotype and increased prolactin secretion in vitro in estrogen-pretreated cells of both genotypes. But conditioned media from D2R−/− cells enhanced human umbilical vein cell proliferation, and this effect could be partially inhibited by an anti-VEGF antiserum. Finally, using dual-labeling immunofluorescence and confocal laser microscopy, we found that in the hyperplastic pituitaries, VEGF-A was mostly present in follicle-stellate cells. In conclusion, pituitary VEGF expression is under dopaminergic control, and even though VEGF does not promote pituitary cellular proliferation in vitro, it may be critical for pituitary angiogenesis through paracrine actions in the D2R knockout female mice.

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 Estrogen-Induced CCN1 Is Critical for Establishment of Endometriosis-Like Lesions in Mice

2014 ◽  
Vol 28 (12) ◽  
pp. 1934-1947 ◽  
Author(s):  
Yuechao Zhao ◽  
Quanxi Li ◽  
Benita S. Katzenellenbogen ◽  
Lester F. Lau ◽  
Robert N. Taylor ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Tissue Growth ◽  
Endometrial Tissue ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Factor C ◽  
Endothelial Growth Factor

Endometriosis is a prevalent gynecological disorder in which endometrial tissue proliferates in extrauterine sites, such as the peritoneal cavity, eventually giving rise to painful, invasive lesions. Dysregulated estradiol (E) signaling has been implicated in this condition. However, the molecular mechanisms that operate downstream of E in the ectopic endometrial tissue are unknown. To investigate these mechanisms, we used a mouse model of endometriosis. Endometrial tissue from donor mice was surgically transplanted on the peritoneal surface of immunocompetent syngeneic recipient mice, leading to the establishment of cystic endometriosis-like lesions. Our studies revealed that treatment with E led to an approximately 3-fold increase in the lesion size within a week of transplantation. E also caused a concomitant stimulation in the expression of connective tissue growth factor/Cyr61/Nov (CCN1), a secreted cysteine-rich matricellular protein, in the lesions. Interestingly, CCN1 is highly expressed in human ectopic endometriotic lesions. To address its role in endometriosis, endometrial tissue from Ccn1-null donor mice was transplanted in wild-type recipient mice. The resulting ectopic lesions were reduced up to 75% in size compared with wild-type lesions due to diminished cell proliferation and cyst formation. Notably, loss of CCN1 also disrupted the development of vascular networks in the ectopic lesions and reduced the expression of several angiogenic factors, such as vascular endothelial growth factor-A and vascular endothelial growth factor-C. These results suggest that CCN1, acting downstream of E, critically controls cell proliferation and neovascularization, which support the growth and survival of endometriotic tissue at ectopic sites. Blockade of CCN1 signaling during the early stages of lesion establishment may provide a therapeutic avenue to control endometriosis.

scholarly journals Rac1-Dependent Intracellular Superoxide Formation Mediates Vascular Endothelial Growth Factor–Induced Placental Angiogenesis in Vitro

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5315-5325 ◽  
Author(s):  
Su-min Li ◽  
Ling-wen Zeng ◽  
Lin Feng ◽  
Dong-bao Chen
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Vascular Endothelial ◽  
Oxidase System ◽  
Placental Angiogenesis ◽  
Superoxide Formation ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is one of the best characterized angiogenic factors controlling placental angiogenesis; however, how VEGF regulates placental angiogenesis has not yet completely understood. In this study, we found that all the components of assembling a functional NADPH oxidase (NOX2, p22phox, p47phox, p67phox, and Rac1) are expressed in ovine fetoplacental artery endothelial cells (oFPAECs) in vitro and ex vivo. Treatment with VEGF (10 ng/ml) rapidly and transiently activated Rac1 in oFPAECs in vitro and increased Rac1 association with p67phox in 5 min. Intracellular superoxide formation began to significantly increase after 25–30 min of VEGF stimulation, which was mediated by both VEGFR1 and VEGFR2. VEGF also stimulated oFPAE cell proliferation and migration and enhanced the formation of tube-like structures on Matrigel matrix. In oFAPEC transfected with specific Rac1 small interfering RNA (siRNA, 40 nm), VEGF-induced intracellular superoxide formation was completely abrogated in association with a 78% reduction of endogenous Rac1. In oFPAE cells transfected with the specific Rac1 siRNA, but not with transfection reagent alone or scrambled control siRNA, VEGF-induced cell proliferation, migration, and tube-like structure formation were dramatically inhibited. Pretreatment of an NADPH oxidase inhibitor apocynin also abrogates the VEGF-stimulated intracellular superoxide production and DNA synthesis in oFPAECs. Taken together, our results demonstrated that a Rac1/Nox2-based NADPH oxidase system is present in placental endothelial cells. This NADPH oxidase system appears to generate the second messenger superoxide that plays a critical role in the signaling control of the VEGF-induced placental angiogenesis.

scholarly journals Correlation of endothelial cell proliferation with vascular endothelial growth factor in endometrium of women with menorrhagia

2017 ◽  
Vol 5 (5) ◽  
pp. 2034
Author(s):  
Kiran B. Mehra ◽  
Nitin M. Gangane ◽  
Deepti R. Joshi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Endothelial Cell Proliferation ◽  
P Value ◽  
Vascular Endothelial ◽  
Luminal Surface ◽  
Vegf Expression ◽  
Secretory Phase ◽  
Endothelial Proliferation ◽  
Endothelial Growth Factor

Background: Approximately 30% of women of reproductive age experience excessive blood loss during menstruation. In 50% of cases, menorrhagia has no underlying pathology. However, until recently, the only permanent cure for menorrhagia was hysterectomy. In this study we aim to determine the correlation of vascular endothelial growth factor (VEGF) expression with markers of endometrial endothelial cell proliferation like proliferating cell nuclear antigen (PCNA) and Cluster Determination (CD34).Methods: A total of 100 patients with history of menorrhagia were selected for study. Double Immunohistochemistry was performed on these endometrial biopsy sections. Proliferating endothelial cells were identified by an immunohistochemical double staining technique with PCNA and CD34. VEGF expression was also seen in endometrial biopsy.Results: In general, expression of both VEGF and PCNA was more in functional layer than basal layer in both menorrhagic patients as well as non menorrhagic patients.  When glandular cytoplasmic VEGF expression was compared with PCNA the association was statistically significant whereas completely opposite findings was seen with glandular luminal surface VEGF positivity but the association was statistically significant. In secretory phase (p-value<0.001) there was highly statistically significant association in PCNA grading with glandular luminal surface VEGF positivity whereas when we correlated PCNA with  cytoplasmic  glandular VEGF in secretory phase it was statistically significant (p-value<0.001).Conclusions: The endothelial proliferation was significantly higher in menorrhagia patients during late secretory phase of cycle than controls. We were able to demonstrate increased endothelial proliferation in patients in the premenstrual part of cycle.

Hypoxia-inducible expression of vascular endothelial growth factor for the treatment of spinal cord injury in a rat model

2007 ◽  
Vol 7 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Byung Hyune Choi ◽  
Yoon Ha ◽  
Xian Huang ◽  
So Ra Park ◽  
Joonho Chung ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vascular Endothelial Growth Factor ◽  
Expression System ◽  
Control Group ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Endothelial Growth Factor

Object Vascular endothelial growth factor (VEGF) has been investigated as a therapy for many disorders and injuries involving ischemia. In this report, we constructed and evaluated a hypoxia-inducible VEGF expression system as a treatment for spinal cord injury (SCI). Methods The hypoxia-inducible VEGF plasmid was constructed using the erythropoietin (Epo) enhancer with the Simian virus 40 (SV40) promoter (pEpo-SV-VEGF) or the RTP801 promoter (pRTP801-VEGF). The expression of VEGF in vitro was evaluated after transfection into N2A cells. The plasmids were then injected into rat spinal cords with contusion injuries. The expression of VEGF in vivo was measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Locomotor recovery in the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale for locomotor analysis. Results In vitro transfection showed that pEpo-SV-VEGF or pRTP801-VEGF induced VEGF expression under hypoxic conditions, whereas pSV-VEGF did not. The VEGF level was higher in the pEpo-SV-VEGF and pRTP801-VEGF groups than in the control group. The VEGF expression was detected in neurons and astrocytes of the spinal cord. Locomotor recovery was improved in the pEpo-SV-VEGF and pRTP801-VEGF groups, and BBB scores were higher than in the control group. Staining using terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling showed that the number of apoptotic cells decreased in the plasmid-injected groups compared with the control group, and significant differences were observed between the hypoxia-responsive groups and the pSV-VEGF group. Conclusions These results suggest that the hypoxia-inducible VEGF expression system may be useful for gene therapy of SCI.

S1577 Endothelin Inhibits Both In Vivo and In Vitro Cholangiocarcinoma Growth By a Decrease in Vascular Endothelial Growth Factor (VEGF) Expression

2009 ◽  
Vol 136 (5) ◽  
pp. A-817
Author(s):  
Giammarco Fava ◽  
Sharon DeMorrow ◽  
Heather Francis ◽  
Eugenio Gaudio ◽  
Paolo Onori ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

scholarly journals The Antiangiogenic Effect of Sanguinarine Chloride on Experimental Choroidal Neovacularization in Mice via Inhibiting Vascular Endothelial Growth Factor

2021 ◽  
Vol 12 ◽  
Author(s):  
Junxiu Zhang ◽  
Ke Mao ◽  
Qing Gu ◽  
Xingwei Wu
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Antiangiogenic Effect ◽  
Laser Injury ◽  
Endothelial Growth Factor

Background: The purpose of this study is to investigate the antiangiogenic effect of Sanguinarine chloride (SC) on models of age-related macular degeneration (AMD) both in vivo and in vitro.Methods: Choroidal neovascularization (CNV) was conducted by laser photocoagulation in C57BL6/J mice. SC (2.5 μM, 2 μl/eye) was intravitreally injected immediately after laser injury. The control group received an equal amount of PBS. 7 days after laser injury, CNV severity was evaluated using fundus fluorescein angiography, hematoxylin and eosin (H&amp;E) staining, and choroid flat-mount staining. Vascular endothelial growth factor (VEGF) expression in the retina/choroid complex was measured by western blot analysis and ELISA kit. In vitro, human retinal microvascular endothelial cells (HRMECs) were used to investigate the effects of SC on cell tube formation, migration, and cytotoxicity. The expression of VEGF-induced expression of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (AKT), mitogen-activated protein kinases (p38-MAPK) in vitro and laser induced VEGF expression in vivo were also analyzed.Results: SC (≤2.5 μM) was safe both in vitro and in vivo. Intravitreal injection of SC restrained the formation of laser induced CNV in mice and decreased VEGF expression in the laser site of the retina/choroid complex. In vitro, SC inhibited VEGF-induced tube formation and endothelial cell migration by decreasing the phosphorylation of AKT, ERK1/2, and p38-MAPK in HRMECs.Conclusions: SC could inhibit laser-induced CNV formation via down-regulating VEGF expression and restrain the VEGF-induced tube formation and endothelial migration. Therefore, SC could be a potential candidate for the treatment of wet AMD.

Sign in / Sign up

Export Citation Format

Share Document