| Project/Area Number |
25460263
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ICHISE Taeko 東京大学, 医科学研究所, 助教 (00396863)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | マウス / Ras / Erk / リンパ管 / 内皮間葉移行 / 表皮 / Raf / PI3キナーゼ / RalGEF / 皮膚表皮 / トランスジェニックマウス / MAPキナーゼ / リンパ管内皮細胞 |
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| Outline of Final Research Achievements |
Recent studies have demonstrated that endothelial-to-mesenchymal transition (EndMT) is implicated in human diseases. However, the molecular basis of EndMT remains largely unknown. We found that α-smooth muscle actin-positive lymphatic endothelial cells (LECs) appear in mouse lymphedematous skin in vivo. Mouse immortalized LECs lost their characteristics and underwent EndMT when cultured in FGF2-depleted medium in vitro. FGF2 depletion acted synergistically with TGFβ to induce EndMT. In contrast, H-Ras-overexpressing LECs were resistant to EndMT. Activation of Ras not only upregulated FGF2-induced activation of the Erk MAP kinases and LEC-specific gene expression, but also suppressed TGFβ-induced activation of Smad2 by modulating Smad2 phosphorylation by Erk MAPKs. Our findings provide a new insight into the FGF2-Ras-MAPK-dependent mechanism that maintains and modulates the LEC trait.
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