%0 Journal Article %J Science (80- ) %D 1997 %T Hyperplasia of lymphatic vessels in VEGF-C transgenic mice %A Jeltsch, M %A Kaipainen, A %A Joukov, V %A Meng, X %A Lakso, M %A Rauvala, H %A Swartz, M %A Fukumura, D %A Jain, R K %A Alitalo, K %X No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis. %B Science (80- ) %V 276 %P 1423 - 5 %8 1997/May/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/9162011 %N 5317 %! Science %0 Journal Article %J J Cell Physiol %D 1997 %T Vascular endothelial growth factors VEGF-B and VEGF-C %A Joukov, V %A Kaipainen, A %A Jeltsch, M %A Pajusola, K %A Olofsson, B %A Kumar, V %A Eriksson, U %A Alitalo, K %B J Cell Physiol %V 173 %P 211 - 5 %8 1997/Nov/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/9365524 %N 2 %! Journal of Cellular Physiology %0 Journal Article %J Development %D 1996 %T VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development %A Kukk, E %A Lymboussaki, A %A Taira, S %A Kaipainen, A %A Jeltsch, M %A Joukov, V %A Alitalo, K %X The vascular endothelial growth factor family has recently been expanded by the isolation of two new VEGF-related factors, VEGF-B and VEGF-C. The physiological functions of these factors are largely unknown. Here we report the cloning and characterization of mouse VEGF-C, which is produced as a disulfide-linked dimer of 415 amino acid residue polypeptides, sharing an 85% identity with the human VEGF-C amino acid sequence. The recombinant mouse VEGF-C protein was secreted from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30-32x10(3) Mr and 22-23x10(3) Mr which preferentially stimulated the autophosphorylation of VEGFR-3 in comparison with VEGFR-2 (KDR). In in situ hybridization, mouse VEGF-C mRNA expression was detected in mesenchymal cells of postimplantation mouse embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions. In addition, the developing mesenterium, which is rich in lymphatic vessels, showed strong VEGF-C expression. VEGF-C was also highly expressed in adult mouse lung, heart and kidney, where VEGFR-3 was also prominent. The pattern of expression of VEGF-C in relation to its major receptor VEGFR-3 during the sprouting of the lymphatic endothelium in embryos suggests a paracrine mode of action and that one of the functions of VEGF-C may be in the regulation of angiogenesis of the lymphatic vasculature. %B Development %V 122 %P 3829 - 37 %8 1996/Dec/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/9012504 %N 12 %! Development (Cambridge, England)