| Project/Area Number |
18K07420
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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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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
NISHIO KENJI 奈良県立医科大学, 医学部, 教授 (60254489)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 腎虚血再灌流傷害 / VWF / ADAMTS13 / 癌細胞 / 血小板 / 癌 / 腎臓 / LLC細胞 / UL-VWF / 血管内皮細胞 / 肺がん細胞 / cancer |
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| Outline of Final Research Achievements |
1.We compared renal ischemia-reperfusion injury in wild type mice (WT) and VWF gene-deleted mice (VWF-KO).In WT mice, renal blood flow at 24 hours after reperfusion was decreased, serum Cr was increased, and tubular damage was stronger in tissues than in VWF-KO, suggesting that VWF is involved in the worsening of renal ischemia-reperfusion injury. In WT mice, recombinant ADAMTS13 improved ischemia-reperfusion injury, suggesting that VWF causes microthrombosis and leukocyte adhesion in renal ischemia-reperfusion injury, and that modulating VWF function by ADAMTS13 may be a means of preventing or treating renal ischemia-reperfusion injury.
2.When LLC lung cancer cells were flowed with washed platelets onto VWF secreted from cultured vascular endothelial cells under flow conditions, the lung cancer cells adhered to VWF and platelets in the presence of ADP.
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| Academic Significance and Societal Importance of the Research Achievements |
腎機能障害は低酸素、低潅流、薬剤性や各種疾患にて惹起される。その一つである腎虚血再灌流傷害をVWFは惹起、増大させる因子であることが示され、VWFの機能を制御するADAMTS13が虚血再灌流傷害を減少させることが証明された。このことにより、ADAMTS13の投与により腎移植後の腎機能が現状よりもより温存される可能性が示唆され、社会的意義は大きいと考える。
また、血管内皮細胞より分泌されたVWFに血小板とADP存在下に癌細胞が粘着することを観察した。VWFの機能を制御するADAMTS13の機能を考えると、ADAMTS13が癌の転移を抑制する可能性を示していると考える。
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