| 초록 |
To regulate the immense spectrum of these biochemical reactions, hepatocytes are efficiently specialized for different metabolic processes depending on the spatial location. The generation of toxic intermediate depending on zonal regions have been overlooked in vitro. In this study, we investigated how intercellular Wnt/β-catenin signaling in the liver lobule, affects activity levels of cytochrome P450 that are involved in drug metabolism. Furthermore, we also designed a system for drug toxicity to mimic the liver zonation by generating a gradient of CHIR99021, β-catenin signaling stablizer, through agarose channel containing HepaRG cells. Upon dividing the channel system into three zone, HepaRG cells in each zone showed different protein signal profiles after being treated by acetaminophen. This work was supported by a grant (2017R1D1A1B03035898, NRF-2016M3A9C4953144) from the Ministry of Science and ICT and a general research grant from the Korea Institute of Toxicology. |
