2007 Fiscal Year Final Research Report Summary
Molgoilar regulation promoting cellular motility in human lymphatic endothelial cells in the skin
| Project/Area Number |
18591251
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Ehime University |
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Principal Investigator |
MURAKAMI Shinji Ehime University, University Hospital, Senior Assistant Professor (50175626)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAKAWA Satoshi Ehime University, University Hospital, Senior Assistant Professor (50419511)
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| Project Period (FY) |
2006 – 2007
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| Keywords | anmogenesis / gene expression / cell motility / tissue and regulation / transcription factor |
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| Research Abstract |
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.
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[Journal Article] VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites2007
Author(s)
Hirakawa, S, Brown, LF., Kodama, S, Paavonen, K, Alitalo, K, Detmar, M
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Journal Title
Blood 109
Pages: 1010-1017
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] STAT5aIPPARgamma pathway regulates involucrin expression in keratinocyte differentiation2007
Author(s)
Dai, X, Sayama, K, Shirakata, Y, Hanakawa, Y, Yamasaki, K, Tokumaru, S, Yang, L, Wang, X, Hirakawa, S, Tohyama, M, Yamauchi, T, Takashi, K, Kagechika, H, Hashimoto, K
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Journal Title
Jinvest Dermatol 127
Pages: 1728-35
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Suppressor of cytokine signaling 3 negative regulation of signal transducer and activator of transcription 3 in platelet-derived growth factor-induced fibroblast migration2007
Author(s)
Nagai, H, Tokumaru, S, Sayama, K, Shirakata, Y, Hanakawa, Y, Hirakawa, S, Dai, X, Tohyama, M, Yang, L, Hashimoto, K
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Journal Title
J Dermatat 34
Pages: 523-530
Description
「研究成果報告書概要(欧文)」より
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[Book] Dermatology2008
Author(s)
Detmar M, Hirakawa S.
Total Pages
1553-1564
Publisher
MOSBY ELSEVIER
Description
「研究成果報告書概要(和文)」より
