Search for the factors enhancing human hepatocyte function based on the unraveling of the transcriptional regulation of marker genes

Research Project

Project/Area Number	17K15515
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Medical pharmacy
Research Institution	University of Shizuoka
Principal Investigator	Hosaka Takuomi 静岡県立大学, 薬学部, 助教 (30611579)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000) Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	肝細胞 / CYP3A4 / 栄養素 / アミノ酸 / 遺伝子発現 / 肝臓 / 肝分化マーカー / 腸内細菌代謝産物 / 肝実質細胞 / 肝非実質細胞
Outline of Final Research Achievements	In this study, we searched for nutrients that increase the expression of a hepatic drug-metabolizing enzyme CYP3A4 as an indicator of enhancement of human hepatocyte function. The results indicated that a mixture of essential amino acids or non-essential amino acids increases CYP3A4 expression level in a human liver-derived cell line HepG2 in a dose-dependent manner. Furthermore, it was suggested that the increase is not attributed to the activation of the amino acid-sensing mTOR pathway or the pregnane X receptor that is known to be involved in CYP3A4 induction, indicating the existence of an unknown mechanism.
Academic Significance and Societal Importance of the Research Achievements	現在、ヒトiPS細胞から肝細胞様細胞を作製することは可能であるが、その肝機能は未熟であるため創薬研究に応用可能なレベルではない。本研究成果より、培地中のアミノ酸組成を最適化することがヒトiPS細胞由来の肝細胞様細胞の肝機能を高めることにつながると期待される。