| Project/Area Number |
15K09639
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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 |
Pediatrics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAGASAWA Masayuki 東京医科歯科大学, 医学部附属病院, 非常勤講師 (90262196)
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| Co-Investigator(Kenkyū-buntansha) |
西村 良成 金沢大学, 附属病院, 講師 (50324116)
松本 雅則 奈良県立医科大学, 医学部, 教授 (60316081)
矢部 普正 東海大学, 医学部, 講師 (70220217)
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| Project Period (FY) |
2015-10-21 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | トロンボモジュリン / 慢性GVHD / 炎症 / 造血幹細胞移植 / 慢性GvHD / 凝固 / サイトカイン / 血管内皮障害 / GvHD / 調節性T細胞 / PRDX2 / Calpain / 酸化ストレス / Band3 / microparticle |
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| Outline of Final Research Achievements |
We investigated the effect of thrombomodulin (TM) in the chronic inflammation by using a mouse chronic GvHD model. TM improved the skin lesion of chronic GvHD and chronic GvHD score significantly. This effect worked well prophylactically but not therapeutically. Dalteparin or activated protein C could not present these effects, which indicated the effect of TM on the chronic inflammation was not dependent on anti-coagulation or activated protein C activity. The number of regulatory B cells and regulatory T cells and the production of TNF-α、INF-γ、IL17A in the spleen cells were not different between TM-treated and control mice. TM is composed of lectin-like domain (D1), EGF-like domain (D2) and serine/threonine-rich domain (D3). To further study the mechanism of TM function on the chronic inflammation, D123, D1, D2, and D23 mutant TM were successfully constructed by using the yeast expression system. We are planning to study by using these mutants.
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