| Project/Area Number |
16K08614
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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 |
Pathological medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
WATABE Tetsuro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00334235)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | リンパ管内皮細胞 / 内皮間葉移行 / TGF-β / TNF-α / 浮腫 / 老化 / 血管内皮細胞 / リンパ管 / 血管 / 循環器 / シグナル伝達 |
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| Outline of Final Research Achievements |
Lymphatic systems play important roles in the maintenance of fluid homeostasis and undergo anatomical and physiological changes during inflammation and ageing. While lymphatic endothelial cells (LECs) undergo mesenchymal transition in response to transforming growth factor-β (TGF-β), the molecular mechanisms underlying EndMT of LECs remain largely unknown. In this study, we examined the effect of TGF-β2 and tumor necrosis factor-α (TNF-α), an inflammatory cytokine, on EndMT using human skin-derived lymphatic endothelial cells (HDLECs). TGF-β2-treated HDLECs showed increased expression of SM22α, a mesenchymal cell marker accompanied by increased cell motility and vascular permeability, suggesting HDLECs to undergo EndMT. Our data also revealed that TNF-α could enhance TGF-β2-induced EndMT of HDLECs. Furthermore, both cytokines induced the production of Activin A while decreasing the expression of its inhibitory molecule Follistatin, and thus enhancing EndMT.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究から期待される成果は学術的（基礎生物学）そして社会的（臨床応用）など多岐に渡って大きな意義を有する。まず基礎生物学に関してだが、本研究成果により、リンパ管内皮細胞のEndMTがTGF-βにより協調的に誘導されることを明らかにした点で意義は大きい。また、この研究成果の臨床医学における意義としては、TGF-β阻害剤などを用いたEndMTを標的とした老年性リンパ浮腫の治療法開発が期待されるという点が挙げられる。さらに、本研究成果によって得られる知見はEndMTのみならず、リンパ管疾患における治療の新たな標的につながる可能性が高く、社会的意義は大きい。
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