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Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.
Gene References into Functions
As shown in mouse model of kidney fibrosis CTGF is significantly involved in fibrosis-associated renal lymphangiogenesis through regulation of, and direct interaction with, VEGF-C. PMID: 28545716
Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, independently of its ligand, VEGF-C, in the uterus during pregnancy. PMID: 28849193
A novel heparin conjugate (LHbisD4) is shown to prevent lymphangiogenesis by blocking the vascular endothelial growth factor C (VEGF-C) induced signaling pathway. PMID: 28586719
lymphangiogenesis is regulated by two distinct proteolytic mechanisms of ligand activation: one in which VEGFC activation by ADAMTS3 and CCBE1 spatially and temporally patterns developing lymphatics, and one in which VEGFD activation by a distinct proteolytic mechanism may be stimulated during inflammatory lymphatic growth PMID: 27159393
These results reveal an unexpected role for VEGF-C, a major lymphangiogenic growth factor, in the transition to fetal liver erythropoiesis. PMID: 27343251
Data show that in the MCF-7 breast cancer cell line, only MT1X metallothioneins (MTs) positively correlated with vascular endothelial growth factor C (VEGFC). PMID: 27107086
The authors show that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. PMID: 26459520
MT1-MMP directly cleaves LYVE-1 on lymphatic endothelial cells to inhibit LYVE-1-mediated lymphangiogenic responses and restrains the production of VEGF-C. PMID: 26926389
Results showed that the VEGF-C/VEGFR-3 system underlies the protective effect of ischemic preconditioning against forebrain ischemia in the mouse hippocampus PMID: 25637798
Vascular endothelial growth factor C/VEGFR-3 signaling modifies HS and CCL21 gradients around lymphatics, regulating lymphocyte migration. PMID: 25606800
Coronary artery stem development first requires VEGF-C to stimulate vessel growth around the outflow tract. PMID: 25271623
Data show that the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE 1) was similar with vascular endothelial growth factor C (VEGF-C), but its peak appeared 1-2 d later than that of VEGF-C. PMID: 25270205
reveal the evolutionary conservation of the lymphatic-like phenotype of the Schlemm's canal (SC), implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis PMID: 25061878
Sinus venosus-derived and endocardial-derived migratory routes unite to form the coronary vasculature, with the former requiring VEGFC - a tissue-specific mediator of blood endothelial development. PMID: 25377552
suggest that correction of defective lymphatic function with VEGF-C has potential as a therapeutic strategy for inflammatory bowel disease. PMID: 25105363
VEGF-C/VEGFR3 signaling plays an important role in the resolution of skin inflammation PMID: 24252749
The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in perinatal development. PMID: 24429550
Our findings indicate that tumors may develop resistance to anti-VEGF therapy by activating the VEGF-C pathway PMID: 24333721
Epidermal keratinocyte proliferation in vitro was not affected by VEGF-C or VEGF-D. PMID: 23695550
VEGFC genetically interacts with Sox17 to regulate lymphangiogenesis in zebrafish. PMID: 23520166
High vascular endothelial growth factor-C leads to tumor lymphangiogenesis and growth of gastric cancer. PMID: 23475632
Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction. PMID: 22932121
VEGF-C promotes immune tolerance in murine melanoma. PMID: 22832193
VEGF-C derived from CD11b(+) cells play a critical role in angiogenesis and lymphangiogenesis in a murine model of hind limb ischemia. PMID: 23219511
Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis. PMID: 23462469
primary tumors -via secretion of VEGF-C- can induce hyperplasia of the sentinel lymph node lymphatic vessel network and thereby promote their further spread. PMID: 23076721
The extent of both lymphatic proliferation and drainage parallels the progression of lesion severity, as does the up-regulation of pro-lymphangiogenic factors VEGF-C, VEGFR-3, ANG-1, and ANG-2. IL-4-stimulated cells PMID: 22574929
new function of CEBP-delta in lymphangiogenesis through regulation of VEGFR3 signaling in lymphatic endothelial cells PMID: 21666710
Data show that that OUBC induces profound lymphangiogenesis in the tumor and SLN and substantial lymphatic metastasis to SLN through VEGF-C/D-VEGFR-3 signaling pathway. PMID: 21481239
VEGF-C binds to heparan sulfate purified from primary lymphatic endothelia PMID: 21343305
AFP mRNA and VEGF-C mRNA in peripheral blood were significantly correlated with recurrence and metastasis of hepatocellular carcinoma. PMID: 20506647
In conclusion, these newly identified VEGF-C isoforms represent a new class of proteins, which are potentially involved in epithelial cell adhesion and proliferation through novel receptor pathways. PMID: 20415667
interaction between neuropilin-2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C. PMID: 20065093
Increased level of VEGF-C stimulates cell growth and alters the metastatic pattern of orthotopic prostate tumors. PMID: 19821979
Results identify the IGF-IR as a positive regulator of VEGF-C expression and implicate it in the control of lymphatic metastasis. PMID: 12649170
Data demonstrate the expression of vascular endothelial growth factor receptor-3 and vascular endothelial growth factor-C on corneal dendritic cells, which implicate a potential relationship between lymphangiogenesis and leukocyte trafficking in the eye. PMID: 12819011
VEGF-C is required for sprouting of the first lymphatic vessels from embyronic veins. PMID: 14634646
Forty percent of functional lymphatics with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. These lymphatic vessels displayed a retrograde draining pattern, indicating possible dysfunction of the intraluminal valves. PMID: 15231646
VEGF-C and VEGF-D are ligands for the integrin alpha9beta1 PMID: 15590642
Overexpression of VEGF-C causes transient lymphatic hyperplasia but not increased lymphangiogenesis in regenerating skin. PMID: 15890974
VEGF-C expression peaked at the initiation of lymphangiogenesis but was reduced to lower levels throughout organization and maturation. PMID: 16648194
VEGF-C facilitates lymphatic metastasis by increasing the delivery of cancer cells to lymph nodes. PMID: 16912183
results suggest the presence of lymphatic capillaries throughout the skeletal muscle, and present the localisation of VEGF-C and -D in the muscles PMID: 16924525
important role of VEGF-C-induced lymph node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel lymph nodes. PMID: 17032920
Chy-3 mice carry a large chromosomal deletion that includes Vegfc; phenotype includes a hypoplastic dermal lymphatic network, a lateral lymphatic pathway directly connecting the inguinal to the axillary lymph node, lower limb lymphatic abnormalities . PMID: 17584866
VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. PMID: 17766486
VEGF-C is a new RANKL target gene in osteoclasts and functions as an autocrine factor regulating osteoclast activity PMID: 18359770
These results suggest VEGF-C- and VEGF-D-independent functions for VEGFR-3 in the early embryo. PMID: 18519586
activation of VEGF-C-VEGF receptor 3 has critical roles in reconnection of the collecting lymph vessels in adult mice. PMID: 18951277
Data show that blood vessels can undergo VEGF-C-induced angiogenesis even after down-regulation of VEGFR-3 in embryos; but transient VEGF-C expression in adults can induce long-lasting lymphatic hyperplasia with no side effects on blood vasculature. PMID: 18988807
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Subcellular Location
Secreted.
Protein Families
PDGF/VEGF growth factor family
Tissue Specificity
Expressed in adult heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis and intestine with higher levels in heart, brain and kidney. Isoform 4 levels are very low. Isoform 3 is mostly expressed in liver and has reduced expression level in ot