Gene Symbol: Vegfc
Description: vascular endothelial growth factor C
Alias: AW228853, VEGF-C, vascular endothelial growth factor C, VRP, flt4 ligand, flt4-L, vascular endothelial growth factor C isoform 129, vascular endothelial growth factor C isoform 184, vascular endothelial growth factor-related protein
Species: mouse
Products:     Vegfc

Top Publications

  1. Hoshida T, Isaka N, Hagendoorn J, di Tomaso E, Chen Y, Pytowski B, et al. Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. Cancer Res. 2006;66:8065-75 pubmed
  2. Tang Y, Zhang D, Fallavollita L, Brodt P. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Res. 2003;63:1166-71 pubmed
    ..6% reduction) and PD98059 (38% reduction). The results identify the IGF-IR as a positive regulator of VEGF-C expression and implicate it in the control of lymphatic metastasis. ..
  3. Anisimov A, Alitalo A, Korpisalo P, Soronen J, Kaijalainen S, Leppänen V, et al. Activated forms of VEGF-C and VEGF-D provide improved vascular function in skeletal muscle. Circ Res. 2009;104:1302-12 pubmed publisher
    ..The therapeutic value of intramuscular lymph vessels in draining tissue edema and lymphedema can now be evaluated using this model system. ..
  4. Vlahakis N, Young B, Atakilit A, Sheppard D. The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. J Biol Chem. 2005;280:4544-52 pubmed
    ..The interaction between alpha9beta1 and VEGF-C and/or -D may begin to explain the abnormal lymphatic phenotype of the alpha9 knock-out mice. ..
  5. Isaka N, Padera T, Hagendoorn J, Fukumura D, Jain R. Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function. Cancer Res. 2004;64:4400-4 pubmed
    ..Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels. ..
  6. Karkkainen M, Haiko P, Sainio K, Partanen J, Taipale J, Petrova T, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5:74-80 pubmed
    ..Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development...
  7. Tammela T, Zarkada G, Wallgard E, Murtomäki A, Suchting S, Wirzenius M, et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature. 2008;454:656-60 pubmed publisher
    ..Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors. ..
  8. Hirakawa S, Brown L, Kodama S, Paavonen K, Alitalo K, Detmar M. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood. 2007;109:1010-7 pubmed
    ..VEGF-C is therefore a good target to slow or even prevent the onset of metastasis. ..
  9. Dumont D, Jussila L, Taipale J, Lymboussaki A, Mustonen T, Pajusola K, et al. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 1998;282:946-9 pubmed
    ..5. Thus, VEGFR-3 has an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels. ..

More Information


  1. Böhmer R, Neuhaus B, Bühren S, Zhang D, Stehling M, Böck B, et al. Regulation of developmental lymphangiogenesis by Syk(+) leukocytes. Dev Cell. 2010;18:437-49 pubmed publisher
    ..This mechanism does not involve circulating endothelial progenitor cells and demonstrates the potential of hematopoietic cells to control developmental lymphangiogenesis. ..
  2. Mandriota S, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 2001;20:672-82 pubmed
    ..These mice frequently developed pancreatic lymph node metastases. Our findings demonstrate that VEGF-C-induced lymphangiogenesis mediates tumour cell dissemination and the formation of lymph node metastases. ..
  3. Wong S, Haack H, Crowley D, Barry M, Bronson R, Hynes R. Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res. 2005;65:9789-98 pubmed
    ..These results suggest that tumor-secreted VEGF-C and, to a lesser extent, VEGF-A, are important for inducing prostate cancer intratumoral lymphangiogenesis but are unnecessary for lymph node metastasis. ..
  4. Yuan L, Moyon D, Pardanaud L, Breant C, Karkkainen M, Alitalo K, et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development. 2002;129:4797-806 pubmed
    ..Arteries, veins and larger, collecting lymphatic vessels developed normally, suggesting that neuropilin 2 is selectively required for the formation of small lymphatic vessels and capillaries. ..
  5. Chintala H, Krupska I, Yan L, LAU L, Grant M, Chaqour B. The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling. Development. 2015;142:2364-74 pubmed publisher
    ..These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses. ..
  6. Igarashi Y, Chosa N, Sawada S, Kondo H, Yaegashi T, Ishisaki A. VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes. Int J Mol Med. 2016;37:1005-13 pubmed publisher
    ..Our findings provide new insight into the molecular mechanisms underlying the regenerative ability of MSCs. ..
  7. Haiko P, Makinen T, Keskitalo S, Taipale J, Karkkainen M, Baldwin M, et al. Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol Cell Biol. 2008;28:4843-50 pubmed publisher
    ..Unlike the Vegfr3(-/-) embryos, the Vegfc(-/-); Vegfd(-/-) embryos displayed normal blood vasculature after embryonic day 9.5...
  8. Wang Z, Puri T, Quigg R. Characterization of novel VEGF (vascular endothelial growth factor)-C splicing isoforms from mouse. Biochem J. 2010;428:347-54 pubmed publisher
    ..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. ..
  9. Huang Y, Yang H, Hsu Y, Chiu P, Ou G, Hsu M. Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells. Angiogenesis. 2014;17:407-18 pubmed publisher
    ..Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBP? and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs. ..
  10. Bui H, Enis D, Robciuc M, Nurmi H, Cohen J, Chen M, et al. Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD. J Clin Invest. 2016;126:2167-80 pubmed publisher
    Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. VEGFC is required for lymphatic development, while VEGFD is not...
  11. Chen H, Sharma B, Akerberg B, Numi H, Kivelä R, Saharinen P, et al. The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis. Development. 2014;141:4500-12 pubmed publisher
    ..The absence of VEGFC, which is expressed in the epicardium, dramatically inhibited dorsal and lateral coronary growth but left vessels ..
  12. Furrer K, Rickenbacher A, Tian Y, Jochum W, Bittermann A, Käch A, et al. Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway. Proc Natl Acad Sci U S A. 2011;108:2945-50 pubmed publisher
    ..DOI breaks this restraint through an endothelium-dependent mechanism driven by VEGF. This pathway highlights a target for reversing the age-associated decline in the capacity of the liver to regenerate. ..
  13. van Tuyl M, Groenman F, Wang J, Kuliszewski M, Liu J, Tibboel D, et al. Angiogenic factors stimulate tubular branching morphogenesis of sonic hedgehog-deficient lungs. Dev Biol. 2007;303:514-26 pubmed
    ..Stimulation of vascularization with angiogenic factors such as Fgf2 and Ang1 partially restored tubular growth and branching in Shh-deficient lungs, suggesting that vascularization is required for branching morphogenesis. ..
  14. Alitalo A, Proulx S, Karaman S, Aebischer D, Martino S, Jost M, et al. VEGF-C and VEGF-D blockade inhibits inflammatory skin carcinogenesis. Cancer Res. 2013;73:4212-21 pubmed publisher
    ..Our results support the use of VEGF-C/VEGF-D-blocking agents not only to inhibit metastatic progression, but also during the early stages of tumor growth. ..
  15. Hägerling R, Pollmann C, Andreas M, Schmidt C, Nurmi H, Adams R, et al. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J. 2013;32:629-44 pubmed publisher
    ..Providing new insights into their function, we found vascular endothelial growth factor C (VEGF-C) and the matrix component CCBE1 indispensable for LEC budding and migration...
  16. Kirkin V, Mazitschek R, Krishnan J, Steffen A, Waltenberger J, Pepper M, et al. Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2. Eur J Biochem. 2001;268:5530-40 pubmed
    ..These tools should be useful in analysing the different activities and roles of VEGF-C, VEGF-D and their ligands, and in blocking VEGFR-3-mediated lymphangiogenesis. ..
  17. Hu D, Fukuhara A, Miyata Y, Yokoyama C, Otsuki M, Kihara S, et al. Adiponectin regulates vascular endothelial growth factor-C expression in macrophages via Syk-ERK pathway. PLoS ONE. 2013;8:e56071 pubmed publisher
    ..These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages. ..
  18. Chen H, Poduri A, Numi H, Kivela R, Saharinen P, McKay A, et al. VEGF-C and aortic cardiomyocytes guide coronary artery stem development. J Clin Invest. 2014;124:4899-914 pubmed publisher
    ..Studying this niche for cardiomyocyte development, and its relationship with CAs, has the potential to identify methods for stimulating vascular regrowth as a treatment for cardiovascular disease. ..
  19. Parker M, Linkugel A, Goel H, Wu T, Mercurio A, Vander Kooi C. Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form. Structure. 2015;23:677-87 pubmed publisher
    b>Vascular endothelial growth factor C (VEGF-C) is a potent lymphangiogenic cytokine that signals via the coordinated action of two cell surface receptors, Neuropilin-2 (Nrp2) and VEGFR-3...
  20. Yu S, Lv H, Zhang H, Jiang Y, Hong Y, Xia R, et al. Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway. Biochem Biophys Res Commun. 2017;485:432-439 pubmed publisher
    ..Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell...
  21. Taher M, Nakao S, Zandi S, Melhorn M, Hayes K, Hafezi Moghadam A. Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2. FASEB J. 2016;30:2490-9 pubmed publisher
    ..Taher, M., Nakao, S., Zandi, S., Melhorn, M. I., Hayes, K. C., Hafezi-Moghadam, A. Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2. ..
  22. Carmeliet P, Ng Y, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, et al. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med. 1999;5:495-502 pubmed
  23. Lund A, Durães F, Hirosue S, Raghavan V, Nembrini C, Thomas S, et al. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 2012;1:191-9 pubmed publisher
    ..Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation...
  24. Lohela M, Helotera H, Haiko P, Dumont D, Alitalo K. Transgenic induction of vascular endothelial growth factor-C is strongly angiogenic in mouse embryos but leads to persistent lymphatic hyperplasia in adult tissues. Am J Pathol. 2008;173:1891-901 pubmed publisher
  25. Yao J, Da M, Guo T, Duan Y, Zhang Y. RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice. Tumour Biol. 2013;34:1493-501 pubmed publisher
    ..05). Tumor growth rate and LVD was suppressed in vivo (P<0.05). VEGF-C-shRNA effectively suppressed gastric cancer cell migration in vivo, retards tumorigenicity, and lymphangiogenesis in nude mice. ..
  26. Hagura A, Asai J, Maruyama K, Takenaka H, Kinoshita S, Katoh N. The VEGF-C/VEGFR3 signaling pathway contributes to resolving chronic skin inflammation by activating lymphatic vessel function. J Dermatol Sci. 2014;73:135-41 pubmed publisher
    ..This study provides evidence that VEGF-C/VEGFR3 signaling plays an important role in the resolution of skin inflammation; the regulation of lymphatic function may have a great therapeutic potential in inflammatory skin diseases. ..
  27. Kivela R, Silvennoinen M, Lehti M, Kainulainen H, Vihko V. Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle. Am J Physiol Heart Circ Physiol. 2007;293:H2573-9 pubmed
    ..Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage. ..
  28. Scully K, Skowronska Krawczyk D, Krawczyk M, Merkurjev D, Taylor H, Livolsi A, et al. Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland. Proc Natl Acad Sci U S A. 2016;113:13408-13413 pubmed
  29. Chilov D, Kukk E, Taira S, Jeltsch M, Kaukonen J, Palotie A, et al. Genomic organization of human and mouse genes for vascular endothelial growth factor C. J Biol Chem. 1997;272:25176-83 pubmed
    We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) ..
  30. Watanabe T, Koibuchi N, Chin M. Transcription factor CHF1/Hey2 regulates coronary vascular maturation. Mech Dev. 2010;127:418-27 pubmed publisher
    ..These findings suggest that CHF1/Hey2 regulates the later steps of coronary vascular development in both a myocardial-dependent, non-cell autonomous fashion and likely a vascular cell-specific effect as well. ..
  31. Yonekura H, Sakurai S, Liu X, Migita H, Wang H, Yamagishi S, et al. Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis. J Biol Chem. 1999;274:35172-8 pubmed
    ..Furthermore, antisense inhibition of PlGF protein production lowered the endothelial cell synthesis of DNA under hypoxic conditions. The results suggest that these VEGF family members may also take active parts in angiogenesis. ..
  32. Srinivasan R, Escobedo N, Yang Y, Interiano A, Dillard M, Finkelstein D, et al. The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes Dev. 2014;28:2175-87 pubmed publisher
    ..In this study, we identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1...
  33. Lee Y, Koh G. Coordinated lymphangiogenesis is critical in lymph node development and maturation. Dev Dyn. 2016;245:1189-1197 pubmed publisher
    ..Here, using lymphatic-specific reporters, Prox1-GFP mice and Vegfc+/LacZ mice, we analyzed migration, assembly, and ingrowth of lymphatic endothelial cells (LECs) in LNs ..
  34. Han J, Calvo C, Kang T, Baker K, Park J, Parras C, et al. Vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans. Cell Rep. 2015;10:1158-72 pubmed publisher
    ..These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals. ..
  35. Wierzowiecka B, Gomulkiewicz A, Cwynar Zajac L, Olbromski M, Grzegrzolka J, Kobierzycki C, et al. Expression of Metallothionein and Vascular Endothelial Growth Factor Isoforms in Breast Cancer Cells. In Vivo. 2016;30:271-8 pubmed
    ..The research results may indicate certain correlation between an increased expression of selected MT isoforms and a pro-angiogenic factor VEGF in specific types of breast cancer cells. ..
  36. Kivela R, Havas E, Vihko V. Localisation of lymphatic vessels and vascular endothelial growth factors-C and -D in human and mouse skeletal muscle with immunohistochemistry. Histochem Cell Biol. 2007;127:31-40 pubmed
    ..Our results are the first to suggest the presence of lymphatic capillaries throughout the skeletal muscle, and to present the localisation of VEGF-C and -D in the muscles. ..
  37. Zhang Q, Guo R, Lu Y, Zhao L, Zhou Q, Schwarz E, et al. VEGF-C, a lymphatic growth factor, is a RANKL target gene in osteoclasts that enhances osteoclastic bone resorption through an autocrine mechanism. J Biol Chem. 2008;283:13491-9 pubmed publisher
  38. Liersch R, Hirakawa S, Berdel W, Mesters R, Detmar M. Induced lymphatic sinus hyperplasia in sentinel lymph nodes by VEGF-C as the earliest premetastatic indicator. Int J Oncol. 2012;41:2073-8 pubmed publisher
    ..In cases of tumor-free lymph nodes the increased lymphatic network of sentinel lymph nodes is a very early premetastatic sign and may provide a new prognostic indicator and target for aggressive diseases. ..
  39. Dellinger M, Hunter R, Bernas M, Witte M, Erickson R. Chy-3 mice are Vegfc haploinsufficient and exhibit defective dermal superficial to deep lymphatic transition and dermal lymphatic hypoplasia. Dev Dyn. 2007;236:2346-55 pubmed
    ..We demonstrated that Chy-3 mice carry a large chromosomal deletion that includes Vegfc and narrowed this region by monitoring the heterozygosity of genetic markers...
  40. Maes C, Carmeliet P, Moermans K, Stockmans I, Smets N, Collen D, et al. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech Dev. 2002;111:61-73 pubmed
  41. Carmeliet P, Collen D. Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol. 2000;190:387-405 pubmed
    ..A selected number of molecules that have been studied in the authors' laboratory will be reviewed in more detail. ..
  42. Lucitti J, Tarte N, Faber J. Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation. Am J Physiol Heart Circ Physiol. 2015;309:H1141-50 pubmed publisher
    ..During collateral maturation, CLIC4 deficiency resulted in reduced expression of Vegfr2, Vegfr1, Vegfc, and mural cell markers, but not notch-pathway genes...
  43. Villefranc J, Nicoli S, Bentley K, Jeltsch M, Zarkada G, Moore J, et al. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development. 2013;140:1497-506 pubmed publisher
    b>Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized...
  44. Bultmann Mellin I, Dinger K, Debuschewitz C, Loewe K, Melcher Y, Plum M, et al. Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs. Am J Physiol Lung Cell Mol Physiol. 2017;313:L687-L698 pubmed publisher
  45. Kataru R, Jung K, Jang C, Yang H, Schwendener R, Baik J, et al. Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood. 2009;113:5650-9 pubmed publisher
    ..Concomitantly, the expression of lymphangiogenic growth factors such as vascular endothelial growth factor C (VEGF-C), VEGF-D, and VEGF-A were significantly up-regulated in the inflamed skin, DLNs, and ..
  46. Shi V, Bao L, Chan L. Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model. Microcirculation. 2012;19:567-79 pubmed publisher
    ..Our results provide the first demonstration of inflammation-mediated lymphangiogenesis in AD and that IL-4 triggered macrophage recruitment may be closely linked to this phenomenon. ..
  47. Liu Z, Xu J, Colvin J, Ornitz D. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 2002;16:859-69 pubmed
    ..Signaling to multiple FGFRs positions FGF18 to coordinate chondrogenesis in the growth plate with osteogenesis in cortical and trabecular bone. ..
  48. Baldwin M, Halford M, Roufail S, Williams R, Hibbs M, Grail D, et al. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol Cell Biol. 2005;25:2441-9 pubmed
  49. Hayhurst G, Strick Marchand H, Mulet C, Richard A, Morosan S, Kremsdorf D, et al. Morphogenetic competence of HNF4 alpha-deficient mouse hepatic cells. J Hepatol. 2008;49:384-95 pubmed publisher
    ..We conclude that the lack of epithelialization characteristic of the HNF4 alpha-null embryonic liver is due, at least in part, to non-cell autonomous defects, and that null cells do not suffer intrinsic defects in polarization. ..
  50. Mouta Bellum C, Kirov A, Miceli Libby L, Mancini M, Petrova T, Liaw L, et al. Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85alpha, p55alpha, and p50alpha. Dev Dyn. 2009;238:2670-9 pubmed publisher
    ..Our data suggest that Pik3r1 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis...
  51. Bhuiyan M, Kim J, Hwang S, Lee M, Kim S. Ischemic tolerance is associated with VEGF-C and VEGFR-3 signaling in the mouse hippocampus. Neuroscience. 2015;290:90-102 pubmed publisher
    The functions of vascular endothelial growth factor C (VEGF-C) and the VEGF receptor 3 (VEGFR-3) in the nervous system are not well known...
  52. Jung Y, Lee A, Nguyen Thanh T, Kang K, Lee S, Jang K, et al. Hyaluronan-induced VEGF-C promotes fibrosis-induced lymphangiogenesis via Toll-like receptor 4-dependent signal pathway. Biochem Biophys Res Commun. 2015;466:339-45 pubmed publisher
  53. Tuomela J, Valta M, Seppänen J, Tarkkonen K, Vaananen H, Härkönen P. Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors. BMC Cancer. 2009;9:362 pubmed publisher
  54. Xu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, et al. Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. J Cell Biol. 2010;188:115-30 pubmed publisher
    ..In this study, we show that neuropilin-2 (Nrp2), a transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGF-C), plays an important role in lymphatic vessel sprouting...
  55. Heishi T, Hosaka T, Suzuki Y, Miyashita H, Oike Y, Takahashi T, et al. Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis. Am J Pathol. 2010;176:1950-8 pubmed publisher
    ..These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis. ..
  56. Le Bras B, Barallobre M, Homman Ludiye J, Ny A, Wyns S, Tammela T, et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci. 2006;9:340-8 pubmed
    b>Vascular endothelial growth factor C (VEGF-C) was first identified as a regulator of the vascular system, where it is required for the development of lymphatic vessels. Here we report actions of VEGF-C in the central nervous system...
  57. Ogawa S, Lozach J, Jepsen K, Sawka Verhelle D, Perissi V, Sasik R, et al. A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc Natl Acad Sci U S A. 2004;101:14461-6 pubmed
  58. Yin X, Johns S, Lawrence R, Xu D, Reddi K, Bishop J, et al. Lymphatic endothelial heparan sulfate deficiency results in altered growth responses to vascular endothelial growth factor-C (VEGF-C). J Biol Chem. 2011;286:14952-62 pubmed publisher
    ..Lymphatic heparan sulfate may represent a novel molecular target for therapeutic intervention. ..
  59. Fang S, Nurmi H, Heinolainen K, Chen S, Salminen E, Saharinen P, et al. Critical requirement of VEGF-C in transition to fetal erythropoiesis. Blood. 2016;128:710-20 pubmed publisher
    b>Vascular endothelial growth factor C (VEGF-C) is a major driver of lymphangiogenesis in embryos and adults. Vegfc gene deletion in mouse embryos results in failure of lymphangiogenesis, fluid accumulation in tissues, and lethality...
  60. Tamura T, McMicken H, Smith C, Hansen T. Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal. Biochem Biophys Res Commun. 1997;237:419-22 pubmed
    ..The data indicate that this 78 bp sequence encodes a potential MTS for GR in mice. ..
  61. Kuwahara G, Nishinakamura H, Kojima D, Tashiro T, Kodama S. Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia. J Vasc Surg. 2013;57:1090-9 pubmed publisher
    ..Consequently, treatment with self-CD11b(+) cells accelerated recovery from ischemia and may be a promising therapeutic strategy for peripheral arterial disease patients. ..
  62. Goldman J, Le T, Skobe M, Swartz M. Overexpression of VEGF-C causes transient lymphatic hyperplasia but not increased lymphangiogenesis in regenerating skin. Circ Res. 2005;96:1193-9 pubmed
  63. Fitz L, Morris J, Towler P, Long A, Burgess P, Greco R, et al. Characterization of murine Flt4 ligand/VEGF-C. Oncogene. 1997;15:613-8 pubmed
    ..cloning of the murine cDNA, the orthologue of human vascular endothelial growth factor-C and vascular endothelial growth factor related protein. The murine flt4-L gene was localized to chromosome 8 and demonstrated to be widely ..
  64. Lee A, Lee J, Jung Y, Kim D, Kang K, Lee S, et al. Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction. Kidney Int. 2013;83:50-62 pubmed publisher
    ..Additionally, the blockade of VEGF-C and VEGF-D signaling decreased obstruction-induced lymphangiogenesis. Thus, VEGF-C and VEGF-D are associated with lymphangiogenesis in the fibrotic kidney in a mouse model of ureteral obstruction. ..
  65. Kukk E, Lymboussaki A, Taira S, Kaipainen A, Jeltsch M, Joukov V, et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development. 1996;122:3829-37 pubmed
  66. Iwami D, Brinkman C, Bromberg J. Vascular endothelial growth factor c/vascular endothelial growth factor receptor 3 signaling regulates chemokine gradients and lymphocyte migration from tissues to lymphatics. Transplantation. 2015;99:668-77 pubmed publisher
    ..b>Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 (VEGFR-3) are the major lymphatic growth factor ..
  67. D Alessio S, Correale C, Tacconi C, Gandelli A, Pietrogrande G, Vetrano S, et al. VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease. J Clin Invest. 2014;124:3863-78 pubmed publisher
    ..Together, these findings shed light on the contribution of lymphatics to the pathogenesis of gut inflammation and suggest that correction of defective lymphatic function with VEGF-C has potential as a therapeutic strategy for IBD. ..
  68. Li D, Xie K, Ding G, Li J, Chen K, Li H, et al. Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression. Cancer Lett. 2014;346:45-52 pubmed publisher
    ..Our findings indicate that tumors may develop resistance to anti-VEGF therapy by activating the VEGF-C pathway. ..
  69. Becker P, Tran T, Delannoy M, He C, Shannon J, McGrath Morrow S. Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis. PLoS ONE. 2011;6:e27449 pubmed publisher
    ..Defining how Sema3A influences structural plasticity of the developing lung is a critical first step for determining if this pathway can be exploited to develop innovative strategies for repair after acute or chronic lung injury. ..
  70. Lavine K, Long F, Choi K, Smith C, Ornitz D. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development. 2008;135:3161-71 pubmed publisher
    ..Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages. ..
  71. Meng F. [Vascular endothelial growth factor C induces LYVE-1(+) endothelial cells to reconstruct hepatic sinusoid during liver regeneration]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014;30:1039-42 pubmed
    ..VEGF-C induces CD34 positive cells to express LYVE-1 in the reconstruction of hepatic sinusoid, and the cells eventually differentiate into mature hepatic sinusoid endothelial cells. ..
  72. Yao L, Testini C, Tvorogov D, Anisimov A, Vargas S, Baluk P, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014;114:806-22 pubmed publisher
    ..The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in perinatal development. ..
  73. Copeland J, Feng Y, Neradugomma N, Fields P, Vivian J. Notch signaling regulates remodeling and vessel diameter in the extraembryonic yolk sac. BMC Dev Biol. 2011;11:12 pubmed publisher
    ..We propose a role for Notch signaling in elaborating the microenvironment of the nascent arteriole, suggesting novel regulatory connections between Notch signaling and other signaling pathways during endothelial differentiation. ..
  74. Ruiz de Almodovar C, Fabre P, Knevels E, Coulon C, Segura I, Haddick P, et al. VEGF mediates commissural axon chemoattraction through its receptor Flk1. Neuron. 2011;70:966-78 pubmed publisher
    ..Similar to Shh and Netrin-1, VEGF-mediated commissural axon guidance requires the activity of Src family kinases. Our results identify VEGF and Flk1 as a novel ligand/receptor pair controlling commissural axon guidance. ..
  75. Min Y, Ghose S, Boelte K, Li J, Yang L, Lin P. C/EBP-? regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1?. Oncogene. 2011;30:4901-9 pubmed publisher
    ..Blocking HIF-1? activity totally blocked CEBP-?-induced VEGF-C and VEGFR3 expression in LECs. Together, these findings uncover a new function of CEBP-? in lymphangiogenesis through regulation of VEGFR3 signaling in LECs. ..
  76. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  77. Zampell J, Avraham T, Yoder N, Fort N, Yan A, Weitman E, et al. Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines. Am J Physiol Cell Physiol. 2012;302:C392-404 pubmed publisher