Research Project
Grant-in-Aid for Scientific Research (C)
Recent studies indicate a major role of the VEGF-A/VEGFR-2 signaling pathway in lymphangiogenesis. VEGF-A induces proliferation of lymphatic endothelial cells (LEC). However, the mechanism of VEGF-A in LEC migration has not been well characterized. We studied the signal transduction pathway of VEGF-A induced migration in human dermal microvascular lymphatic endotherial cells (HDMLEC) and report here the involvement of signal transducers and activators of transcription 3 (STAT 3) in HDMLEC migration. First, the effect of VEGF on HDMLEC was examined by Boyden chamber assay. VEGF-A enhanced HDMLEC migration in a dose-dependent manner, with a 2 fold optimum at 33ng/ml in 6 hrs. Then, nuclear translocation of phosphorylated STAT3 was assessed by Western Blotting and con-focal microscopy using anti- phosphorylated STAT3 antibody. No phosphorylated STAT3 was observed in nuclei before the addition of 33ng/ml of VEGF-A. However, translocation of phosphorylated STAT3 into nuclei was found 30 min after the addition of VEGF-A and reached an optimum at 60 min. To prove the functional involvement of STAT3 phosphorylation in HDMLEC migration, transfection of dominant negative STAT3 adenovirus vector was performed. Transfection of dominant negative STAT3 adenovirus at M.O.I. of 10 almost completely abolished VEGF-A-induced HDMLEC migration as well as nuclear translocation of phosphorylated STAT3. In conclusion, nuclear translocation of phosphorylated STAT3 is essential for VEGF-A-induced HDMLEC migration.
All 2008 2007 2006
All Journal Article (13 results) (of which Peer Reviewed: 4 results) Presentation (3 results) Book (1 results)
VIOSBY ELSEVIER
Pages: 1553-1564
Blood 109
J Invest Dermatol 127
J Dermatol 34
Pages: 1010-1017
Jinvest Dermatol 127
Pages: 1728-35
J Dermatat 34
Pages: 523-530
10021306180
Blood 109・3
The American Journal of Pathology 169・4
Pages: 1496-1503
Cell and Tissue Research 326・1
Pages: 69-77
The European Journal of Dermatology 16・2
Pages: 141-145
The Journal of Biological Chemistry 281・31
Pages: 22013-22020
