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Characterization of UDP‐glucuronosyltransferase 2B expression and regulation by nuclear signaling pathways in HepaRG cells (1141.6)
Author(s) -
Barrett Kathleen,
DuniecDmuchowski Zofia,
Kocarek Thomas,
RungeMorris Melissa
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1141.6
Subject(s) - pregnane x receptor , farnesoid x receptor , constitutive androstane receptor , nuclear receptor , chemistry , hepatocyte nuclear factor 4 , microbiology and biotechnology , medicine , endocrinology , biology , transcription factor , gene , biochemistry
HepaRG cells are bipotent human liver progenitor cells that can be differentiated into hepatocyte‐like cells that retain important liver functions. We evaluated the expression and regulation of the UDP‐glucuronosyltransferase (UGT) 2B subfamily of conjugating enzymes (UGT2B4, 2B7, 2B10, 2B11, 2B15, 2B17, and 2B28) in HepaRG cells. During proliferative culture conditions, expression of all UGT2Bs increased with cell confluency. After 2% DMSO‐induced differentiation, expression of UGT2B7and 2B17 initially decreased, but levels of all UGT2B mRNAs increased with continued differentiation. Treatment of differentiated HepaRG cells with the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) agonist, phenobarbital, increased expression of all UGT2B genes except UGT2B17. Rifampicin (PXR) increased expression of all UGT2B genes except UGT2B7. CITCO (CAR) increased UGT2B15 and decreased UGT2B17. GW3965 (liver X receptor) decreased all UGT2Bs except UGT2B11, while GW4064 (farnesoid X receptor) increased UGT2B10, 2B11, and 2B15 but decreased UGT2B4, 2B7 and 2B17. Treatment with ciprofibrate (peroxisome proliferator‐activated receptor α) increased UGT2B4, 2B7, and 2B15 but decreased UGT2B10 and 2B17. Treatment with 2,3,7,8‐tetracholorodibenzo‐p‐dioxin (Ah receptor) increased UGT2B4, 2B10, 2B11, 2B15, and 2B28. In conclusion, UGT2B genes are expressed in differentiating HepaRG cells and are differentially regulated by nuclear signaling pathways. Grant Funding Source : Supported by NIH grant ES005823