title: Role of the Drug-Metabolizing Enzyme CYP during Mouse Liver Development.
abstract: The drug-metabolizing enzyme CYP is mainly involved in the metabolism of various substances in the liver, such as drugs, endogenous substances, and carcinogens. Recent reports have also revealed that CYP1B1 plays a major role in the developmental process. Because the level of CYP expression is markedly high in the liver, we hypothesize that CYP plays a role in the developmental process of the liver. To verify this hypothesis, we analyzed the expression patterns of various CYP molecular species and their functions during the differentiation of embryonic stem cells (ES cells) into hepatocytes and the developmental process in mice. The results demonstrated that CYP2R1 and CYP26A1 are expressed at an earlier stage of the differentiation of ES cells into hepatocytes than hepatoblast-specific markers. Additionally, during the development of the mouse liver, CYP2R1 and CYP26A1 were mostly up-regulated during the stage when hepatoblasts appeared. In addition, when CYP2R1 and CYP26A1 expressions were forced in ES cells and liver of adult mice, they differentiated into hepatoblast marker positive cells. These results suggest that CYP2R1 and CYP26A1 may play a major role in hepatoblast cell differentiation during the development of the liver.
authors.affiliation: Department of Clinical Pharmacokinetics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hirose
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kawamura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Komachi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitaoka
authors.forename: Jo
authors.initials: J
authors.lastname: Hatogai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Risako
authors.initials: R
authors.lastname: Kon
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D004247:DNA; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D022781:Hepatocytes / Q000201:enzymology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000196:embryology* / Q000201:enzymology*; D008813:Mice, Inbred ICR; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010957:Plasmids; D011247:Pregnancy; D000072516:Retinoic Acid 4-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D004364:Pharmaceutical Preparations; D004247:DNA; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; C569548:Cyp2r1 protein, mouse; D053493:Cholestanetriol 26-Monooxygenase