scholarly journals Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting

2007 ◽  
Vol 204 (6) ◽  
pp. 1431-1440 ◽  
Author(s):  
Maria Wirzenius ◽  
Tuomas Tammela ◽  
Marko Uutela ◽  
Yulong He ◽  
Teresa Odorisio ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Mouse Skin ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Factor C ◽  
Endothelial Growth Factor

Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent studies suggest that VEGF, which does not bind to VEGFR-3, can also induce lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway that triggers VEGFR-3–independent lymphangiogenesis, we used both transgenic and adenoviral overexpression of placenta growth factor (PlGF) and VEGF-E, which are specific activators of VEGFR-1 and -2, respectively. Unlike PlGF, VEGF-E induced circumferential lymphatic vessel hyperplasia, but essentially no new vessel sprouting, when transduced into mouse skin via adenoviral vectors. This effect was not inhibited by blocking VEGF-C and -D. Postnatal lymphatic hyperplasia, without increased density of lymphatic vessels, was also detected in transgenic mice expressing VEGF-E in the skin, but not in mice expressing PlGF. Surprisingly, VEGF-E induced lymphatic hyperplasia postnatally, and it did not rescue the loss of lymphatic vessels in transgenic embryos where VEGF-C and VEGF-D were blocked. Our data suggests that VEGFR-2 signals promote lymphatic vessel enlargement, but unlike in the blood vessels, are not involved in vessel sprouting to generate new lymphatic vessels in vivo.

scholarly journals Spreds Are Essential for Embryonic Lymphangiogenesis by Regulating Vascular Endothelial Growth Factor Receptor 3 Signaling

2007 ◽  
Vol 27 (12) ◽  
pp. 4541-4550 ◽  
Author(s):  
Koji Taniguchi ◽  
Ri-ichiro Kohno ◽  
Toranoshin Ayada ◽  
Reiko Kato ◽  
Kenji Ichiyama ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Vessels ◽  
Lymphatic Vessels ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Erk Activation ◽  
Factor C ◽  
Endothelial Growth Factor

ABSTRACT Spred/Sprouty family proteins negatively regulate growth factor-induced ERK activation. Although the individual physiological roles of Spred-1 and Spred-2 have been investigated using gene-disrupted mice, the overlapping functions of Spred-1 and Spred-2 have not been clarified. Here, we demonstrate that the deletion of both Spred-1 and Spred-2 resulted in embryonic lethality at embryonic days 12.5 to 15.5 with marked subcutaneous hemorrhage, edema, and dilated lymphatic vessels filled with erythrocytes. This phenotype resembled that of Syk −/− and SLP-76 −/− mice with defects in the separation of lymphatic vessels from blood vessels. The number of LYVE-1-positive lymphatic vessels and lymphatic endothelial cells increased markedly in Spred-1/2-deficient embryos compared with WT embryos, while the number of blood vessels was not different. Ex vivo colony assay revealed that Spred-1/2 suppressed lymphatic endothelial cell proliferation and/or differentiation. In cultured cells, the overexpression of Spred-1 or Spred-2 strongly suppressed vascular endothelial growth factor-C (VEGF-C)/VEGF receptor (VEGFR)-3-mediated ERK activation, while Spred-1/2-deficient cells were extremely sensitive to VEGFR-3 signaling. These data suggest that Spreds play an important role in lymphatic vessel development by negatively regulating VEGF-C/VEGFR-3 signaling.

scholarly journals Topical VEGF-C/D Inhibition Prevents Lymphatic Vessel Ingrowth into Cornea but Does Not Improve Corneal Graft Survival

2020 ◽  
Vol 9 (5) ◽  
pp. 1270
Author(s):  
Ann-Charlott Salabarria ◽  
Manuel Koch ◽  
Alfrun Schönberg ◽  
Elisabeth Zinser ◽  
Deniz Hos ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
High Risk ◽  
Immune Cells ◽  
Lymphatic Vessel ◽  
Corneal Transplantation ◽  
Lymphatic Vessels ◽  
Vascular Endothelial ◽  
Factor C ◽  
Endothelial Growth Factor

Vascular endothelial growth factor-C/D (VEGF-C/D) regulates lymphangiogenesis. Ingrowth of lymphatic vessels is negatively associated with corneal transplantation success. In this study, we therefore analyzed the effect local blockade of VEGF-C/D has on inflamed corneas. We used the murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation. Mice were treated with a VEGF-C/D trap prior to transplantation. Topical inhibition of VEGF-C/D significantly reduced lymphatic vessel ingrowth, but increased Macrophage numbers in the cornea. Furthermore, corneal transplantation success was not improved by the topical application of the compound. This study demonstrates that local VEGF-C/D inhibition is insufficient to increases corneal transplantation success, likely due to interaction with immune cells.

scholarly journals Vascular endothelial growth factor C induces angiogenesis in vivo

1998 ◽  
Vol 95 (24) ◽  
pp. 14389-14394 ◽  
Author(s):  
Y. Cao ◽  
P. Linden ◽  
J. Farnebo ◽  
R. Cao ◽  
A. Eriksson ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Factor C ◽  
Endothelial Growth Factor

Inhibition of Angiogenesis by a Novel Neutralizing Antibody Against Human Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3968-3968
Author(s):  
Hao Chen ◽  
Xiu-Yun Ding ◽  
Yuan Gao ◽  
Fei-Yao Ren ◽  
Hui Li ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Neutralizing Antibody ◽  
Vascular Endothelial ◽  
Hel Cells ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and D (VEGF-D), are the major molecules involved in the development of the embryonic vascular system and pathological lymphangiogenesis. Throughout embryogenesis, VEGFR-3 is expressed in most endothelial cells, whilst being restricted to lymphatic vessels later in development. This receptor plays a significant role in the normal development of blood and lymphatic vessels. In the present studies, we generated a novel panel of 17 monoclonal antibodies (mAbs) against the human VEGFR-3 and characterized their ability to inhibit the proliferation of human erythroleukemia (HEL) cells and angiogenesis of chick embryo chorioallantoic membrane (CAM). Among these mAbs, BDD073 was demonstrated to inhibit the interaction of soluble VEGFR-3 with VEGF-D and the proliferation of HEL cells. In CAM angiogenesis experiments, the angiogenesis induced by recombinant GST-VEGF-D was decreased in the presence of antibody BDD073. These data indicate that this novel neutralizing antibody against human VEGFR-3 not only might be a potential compounds in blocking the VEGF-D-induced angiogenesis and lymphangiogenesis, but also be a tool for the investigations of biology of VEGFR-3 and analysis of lymphatic vessels in malignant tumors and their metastases.

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