We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Role of Nrf2 signaling in development of hepatocyte-like cells.
- Authors
Chie Takasu; Shuhai Chen; Luping Gao; Yu Saito; Yuji Morine; Tetsuya Ikemoto; Shinichiro Yamada; Mitsuo Shimada
- Abstract
Generation of hepatocytes from human adipose-derived mesenchymal stem cells (hADSCs) could be a promising alternative source of human hepatocytes. However, mechanisms to differentiate hepatocytes from hADSCs are not fully elucidated. We have previously demonstrated that our three-step differentiation protocol with glycogen synthase kinase (GSK) 3 inhibitor was effective to improve hepatocyte functions. In this study, we investigated the activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) on hADSCs undergoing differentiation to HLC (hepatocyte-like cells). Our three-step differentiation protocol was applied for 21 days (Step 1: day 1-6, Step2: day 6-11, Step3: day 11-21). Our results show that significant nuclear translocation of Nrf2 occurred from day 11 until the end of HLC differentiation. Nuclear translocation of Nrf2 and CYP3A4 activity in the GSK3 inhibitor-treated group was obviously higher than that in Activin A-treated groups at day 11. The maturation of HLCs was delayed in Nrf2-siRNA group compared to control group. Furthermore, CYP3A4 activity in Nrf2-siRNA group was decreased at the almost same level in Activin A-treated group. Nrf2 translocation might enhance the function of HLC and be a target for developing highly functional HLC.
- Subjects
NUCLEAR factor E2 related factor; LIVER cells; MESENCHYMAL stem cells; GLYCOGEN synthase kinase; ACTIVIN
- Publication
Journal of Medical Investigation, 2023, Vol 70, Issue 3/4, p343
- ISSN
1343-1420
- Publication type
Article
- DOI
10.2152/jmi.70.343