| Project/Area Number |
21K14813
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Sultana Halima 東北大学, スマート・エイジング学際重点研究センター, 助教 (50866837)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Vitamin K / Bile acid metabolism / PXR / Bile metabolism / PXR（pregnane X receptor） / メナキノン-4 / 胆汁代謝 |
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| Outline of Research at the Start |
ビタミンK2(VK2)のひとつであるメナキノン-4は核内受容体PXRのリガンドとして働き、胆汁酸代謝関連遺伝子の発現を制御する。我々はヒト型PXRマウスにVK欠乏食を与えると、肝臓での胆汁酸代謝関連タンパク質の発現量が変化し、肝胆汁酸濃度の上昇を見出した。従来、胆汁うっ滞など肝疾患患者では胆汁の分泌不全によりVKを含む脂溶性物質の吸収が低下して、VK欠乏症を起こすことが知られているが、我々の知見から考えると、VK欠乏による胆汁うっ滞がに肝障害を加速度的に増悪させる可能性がある。本研究では、VKのPXRを介した胆汁酸代謝調節の機構を明確にして、VKの新たな役割として肝疾患予防作用を提唱する。
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| Outline of Final Research Achievements |
The purpose of the current study was to reveal the mechanism of Vitamin K on bile acids (BA) metabolism via human PXR. I found that cholic acid (CA) administration for 1 or 2 weeks causes damage to the liver of hPXR female mice. Though ALP level was increased insignificantly, ALT, LAP, AST, total bilirubin, and BA levels were increased significantly in the serum due to CA treatment. Moreover, MK-4 treatment tends to reduce the serum level of ALT, AST, LAP, and total BA in these mice. I found no significant effect of MK-4 treatment on the expression of BA-related genes in these CA-treated mice.
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| Academic Significance and Societal Importance of the Research Achievements |
It was found that VK defficiency is commonly observed in cholestatic liver disease. However,the mechanism of the effect of VK on cholestasis-related liver disease is not revealed yet. This research could reveal the validation of VK treatment on cholestatic liver disease.
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