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

2018 Fiscal Year Final Research Report

• 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
• Keywords: 肝細胞 / CYP3A4 / 栄養素 / アミノ酸

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.

Free Research Field

分子毒性学

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。