Development the culture method for primary hepatocyte to keeping a same response range in vitro and in vivo for exogenous stimulus.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19916
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: Saga University
• Principal Investigator: Tsujita Tadayuki 佐賀大学, 農学部, 講師 (20622046)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: Nrf1 / 低酸素 / 肝細胞

Outline of Final Research Achievements

When we develop a primary hepatocyte in low oxygen condition from the beginning, the cellular motility of final hepatocyte is lower than when we conduct those strategy in normoxic condition. This method provided us to higher sensitivity for exogenous stimulus including oxidative stress and ER stress. In addition, the hepatocyte that was prepared in normoxic condition has lower levels of stress transcriptional factor, Nrf1 and Nrf2. This condition leads the hepatocyte to lower response fate for exogenous stimulus and lower detoxification activity. We have found that the glycomodifier enzyme, PNGase was contributed to controlling Nrf1 protein level during primary hepatocyte preparation in lower oxygen condition.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

10%程度の低酸素下での肝細胞を調整すると、酸化ストレス、小胞体ストレスなどの刺激に対する感受性が鋭敏になることが確認できた。今後、iPSから樹立されたヒト肝細胞を用いて、低酸素下で薬効試験等を行うことで、in vivoとin vitroとの感受性の乖離を減少させることが可能となり、早期に化合物の生体内での代謝評価を実施できると期待される。