| 研究実績の概要 |
VK acts as a ligand of pregnane X receptor (PXR) which is a predominant regulator of CYP7A1- the key enzyme of bile acids (BA) synthesis hence plays a critical role in the metabolism of BA. VK deficiency is commonly observed in cholestasis. However, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Previously, we showed that VK has an anti-inflammatory effect and VK mediated PXR activation modulates genes expression involved in BA synthesis in humanized PXR (hPXR) mice, but not in wild type (WT) mice. The purpose of the current study is to reveal the mechanism of VK on BA synthesis and transportation via human PXR.
In the first year of the project, I found that cholic acid (CA) treatment for both 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 level were increased significantly in the serum due to CA treatment. Furthermore, I found that MK-4 treatment tends to reduce the serum level of ALT, AST, LAP, and total BA in these mice. Unfortunately, I have found no significant effect of MK-4 treatment on the expression of genes related to BA in these CA treated mice.
In the second year of the project, though I found that VK deficiency changed several genes related to the BA metabolism, I could not continue this project research since I moved to another laboratory in Tohoku University. I did not use any of the grant money in this second year of the project. This money will be returned as soon as possible following the proper procedure.
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