2018 Fiscal Year Final Research Report
Analysis of transcriptional regulation of villin in liver
| Project/Area Number |
16K09207
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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 |
Legal medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 肝臓 / ビリン / リトコール酸 |
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| Outline of Final Research Achievements |
To investigate the transcriptional regulation of villin in HepG2 human hepatocarcinoma cells, Luciferase reporter assay was carried out using villin promoter fragments. Transcription factors SRF and TBP transcribed villin via TATA Box/CArG Box locates around -60 bp on villin promoter. These transcriptional factors reduced their transcriptional activity under lithocholic acid stimulation in HepG2 cells. Villin mRNA expression was decreased by SRF knockdown using siRNA, and increased by TBP knockdown. These result suggest that villin transcriptional regulation by SRF and TBP are prevented by lithocholic acid under cholestasis.
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| Free Research Field |
医歯薬学/社会医学/法医学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、リトコール酸刺激下で転写因子SRFおよびTBPの転写活性が低下することが新たに明らかとなった。SRFは細胞形態の維持に必要な多くの遺伝子の発現を司り、TBPは基礎転写に重要な転写因子として知られている。胆汁鬱滞下でこれらの転写因子がリトコール酸の影響を受ける可能性が示唆されたことで、胆汁鬱滞性肝疾患における遺伝子発現調節を理解するのに役立つとともに、新規の治療法の開発につながる可能性が見出された。
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