scholarly journals Localization of Vascular Endothelial Growth Factor (VEGF), VEGF Receptors and Endothelial Cell Markers in Human Fetal Lung In Vitro. • 223

1997 ◽  
Vol 41 ◽  
pp. 40-40
Author(s):  
Michael J. Acarregui ◽  
Kelli L. Goss ◽  
Jeanne M. Snyder
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Fetal Lung ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Cell Markers ◽  
Endothelial Growth Factor ◽  
Human Fetal Lung

scholarly journals Vascular Endothelial Growth Factor Receptors in Human Mesangiumin Vitroand in Glomerular Disease

2000 ◽  
Vol 11 (7) ◽  
pp. 1236-1243 ◽  
Author(s):  
STEPHEN THOMAS ◽  
JOHANN VANUYSTEL ◽  
GABRIELLA GRUDEN ◽  
VERÓNICA RODRÍGUEZ ◽  
DAVINA BURT ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Ex Vivo ◽  
Fold Increase ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Glomerular Diseases ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

Abstract. Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptorsin vitroandex vivoand evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMCin vitroby immunofluorescence and Western blotting. VEGF165induced a dose-responsive increase in3H-thymidine incorporation (25 ng/ml VEGF165: 2.3-fold increase ; 50 ng/ml : 3.8-fold ; 100 ng/ml : 4.8-fold ; 200 ng/ml : 3.4-fold ;P= 0.016) and in cell number (50 ng/ml VEGF165: 1.2-fold increase ; 100 ng/ml : 1.6-fold ; 200 ng/ml : 1.4-fold ;P= 0.005), effects prevented by an anti-VEGF165polyclonal neutralizing antibody (100 μg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF165: 1.4-fold increase). Inex vivoexperiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF165induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.

Aggretin, a snake venom–derived endothelial integrin α2β1 agonist, induces angiogenesis via expression of vascular endothelial growth factor

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2105-2113 ◽  
Author(s):  
Ching-Hu Chung ◽  
Wen-Bin Wu ◽  
Tur-Fu Huang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Angiogenic Effect ◽  
Endothelial Growth Factor

Abstract Aggretin, a collagen-like α2β1 agonist purified from Calloselasma rhodostoma venom, was shown to increase human umbilical vein endothelial cell (HUVEC) proliferation and HUVEC migration toward immobilized aggretin was also increased. These effects were blocked by A2-IIE10, an antibody raised against integrin α2. Aggretin bound to HUVECs in a dose-dependent and saturable manner, which was specifically inhibited by A2-IIE10, as examined by flow cytometry. Aggretin elicited significant angiogenic effects in both in vivo and in vitro angiogenesis assays, and incubation of HUVECs with aggretin activated phosphatidylinositol 3-kinase (PI3K), Akt, and extracellular-regulated kinase 1/2 (ERK1/2); these effects were blocked by A2-IIE10 or vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). The angiogenic effect induced by aggretin may be via the production of VEGF because the VEGF level was elevated and VEGF mAb pretreatment inhibited Akt/ERK1/2 activation as well as the in vivo angiogenesis induced by aggretin. The VEGF production induced by aggretin can be blocked by A2-IIE10 mAb pretreatment. In conclusion, aggretin induces endothelial cell proliferation, migration, and angiogenesis by interacting with integrin α2β1, leading to activation of PI3K, Akt, and ERK1/2 pathways, and the increased expression of VEGF may be responsible for its angiogenic activity.

Fibroblast growth factor 2 induces the precocious development of endothelial cell networks in bovine luteinising follicular cells

2013 ◽  
Vol 25 (2) ◽  
pp. 372 ◽  
Author(s):  
Mhairi Laird ◽  
Kathryn J. Woad ◽  
Morag G. Hunter ◽  
George E. Mann ◽  
Robert S. Robinson
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Fibroblast Growth ◽  
Branch Points ◽  
Progesterone Production ◽  
Endothelial Growth Factor

The transition from follicle to corpus luteum represents a period of intense angiogenesis; however, the exact roles of angiogenic factors during this time remain to be elucidated. Thus, the roles of vascular endothelial growth factor (VEGF) A, fibroblast growth factor (FGF) 2 and LH in controlling angiogenesis were examined in the present study. A novel serum-free luteinising follicular angiogenesis culture system was developed in which progesterone production increased during the first 5 days and was increased by LH (P < 0.01). Blockade of signalling from FGF receptors (SU5402; P < 0.001) and, to a lesser extent, VEGF receptors (SU1498; P < 0.001) decreased the development of endothelial cell (EC) networks. Conversely, FGF2 dose-dependently (P < 0.001) induced the precocious transition of undeveloped EC islands into branched networks associated with a twofold increase in the number of branch points (P < 0.001). In contrast, VEGFA had no effect on the area of EC networks or the number of branch points. LH had no effect on the area of EC networks, but it marginally increased the number of branch points (P < 0.05) and FGF2 production (P < 0.001). Surprisingly, progesterone production was decreased by FGF2 (P < 0.01) but only on Day 5 of culture. Progesterone production was increased by SU5402 (P < 0.001) and decreased by SU1498 (P < 0.001). These results demonstrate that FGF and VEGF receptors play a fundamental role in the formation of luteal EC networks in vitro, which includes a novel role for FGF2 in induction of EC sprouting.

Direct identification of a major autophosphorylation site on vascular endothelial growth factor receptor Flt-1 that mediates phosphatidylinositol 3′-kinase binding

2001 ◽  
Vol 358 (2) ◽  
pp. 465-472 ◽  
Author(s):  
Ying YU ◽  
Jeffrey D. HULMES ◽  
Mark T. HERLEY ◽  
Ronald G. WHITNEY ◽  
John W. CRABB ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Insect Cells ◽  
Pi3 Kinase ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Phosphatidylinositol 3 Kinase ◽  
Endothelial Growth Factor ◽  
Autophosphorylation Site

Progress has been made in our understanding of the mechanism by which the binding of vascular endothelial growth factor (VEGF) to cognate receptors induces a range of biological responses, but it is far from complete. Identification of receptor autophosphorylation sites will allow us to determine how activated VEGF receptors are coupled to specific downstream signalling proteins. In the present study, we have expressed human VEGF receptors in insect cells using the baculovirus expression system, identified a major autophosphorylation site on the VEGF receptor fms-like tyrosine kinase-1 (Flt-1) by HPLC–electrospray ionization (ESI)–MS, and characterized in vitro interactions between Flt-1 and phosphatidylinositol 3′-kinase (PI3-kinase). Infection of High 5 insect cells with Flt-1 recombinant virus resulted in the expression of a 170kDa glycoprotein, which bound VEGF with a Kd of 2×10−10M in intact insect cells. The overexpressed recombinant Flt-1 receptors exhibited tyrosine kinase activity and were constitutively phosphorylated. Analysis of Flt-1 tryptic peptides by HPLC–ESI–MS with selective phosphate ion monitoring identified a hexapeptide (YVNAFK; where single-letter amino-acid code has been used) containing a phosphotyrosine (pTyr) residue at position 1213. Using synthetic phosphopeptides, this pTyr residue was found to be directly involved in the binding of PI3-kinase in vitro even though it did not fall within a consensus pYM/VXM PI3-kinase binding motif. These results suggest that phosphorylated Flt-1 associates with PI3-kinase at pTyr1213 to mediate the activation of this pathway in VEGF signalling.

VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs

2014 ◽  
Vol 307 (3) ◽  
pp. H455-H463 ◽  
Author(s):  
Adama Sidibé ◽  
Helena Polena ◽  
Karin Pernet-Gallay ◽  
Jeremy Razanajatovo ◽  
Tiphaine Mannic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Reproductive Tract ◽  
Cell Junctions ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 ± 0.3, n = 78; and VE-Y685F, 12.48 ± 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary permeability. Furthermore, this knock-in mouse model is of potential interest for further studies of diseases that are associated with abnormal vascular permeability.

scholarly journals Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5423-5433 ◽  
Author(s):  
Baofeng Zhao ◽  
Changzoon Chun ◽  
Zhong Liu ◽  
Mark A. Horswill ◽  
Kallal Pramanik ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract Our previous work has shown that axon guidance gene family Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro. To investigate NogoB-NgBR function in vivo, we cloned the zebrafish ortholog of both genes and studied loss of function in vivo using morpholino antisense technology. Zebrafish ortholog of Nogo-B is expressed in somite while expression of zebrafish NgBR is localized in intersomitic vessel (ISV) and axial dorsal aorta during embryonic development. NgBR or Nogo-B knockdown embryos show defects in ISV sprouting in the zebrafish trunk. Mechanistically, we found that NgBR knockdown not only abolished its ligand Nogo-B–stimulated endothelial cell migration but also reduced the vascular endothelial growth factor (VEGF)–stimulated phosphorylation of Akt and vascular endothelial growth factor–induced chemotaxis and morphogenesis of human umbilical vein endothelial cells. Further, constitutively activated Akt (myristoylated [myr]Akt) or human NgBR can rescue the NgBR knockdown umbilical vein endothelial cell migration defects in vitro or NgBR morpholino-caused ISV defects in vivo. These data place Akt at the downstream of NgBR in both Nogo-B– and VEGF-coordinated sprouting of ISVs. In summary, this study identifies the in vivo functional role for Nogo-B and its receptor (NgBR) in angiogenesis in zebrafish.

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