title: Analysis of CYP2R1 and CYP26A1 Expression Patterns in Regeneration in Mice with Liver Injury.
abstract: Cytochrome P450 enzymes (CYPs) are involved in the metabolism of various substances in the liver and small intestine and show markedly higher expression levels in the liver compared to other organs. The liver exhibits a remarkable capacity to regenerate. After excision of 70% of the liver, the organ can regenerate to its original size in approximately 1 week. Unlike the normal liver, in the injured liver, hepatic stem cells known as oval cells are considered to play an important role in regeneration. However, the role of CYPs in liver regeneration remains unclear. In the present study, we investigated the role of CYPs in the regeneration of injured liver. Liver injury was induced by 4-week repeated doses of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in the diet. Next, both DDC-fed mice and control diet (containing no DDC)-fed mice were subjected to 70% hepatectomy, and the hepatic gene expression patterns measured during regeneration were analyzed. Mice with DDC-induced liver injury expressed the oval cell markers cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM), and partial hepatectomy increased the expression levels of CYP2R1 and CYP26A1 as well as the hepatoblast marker alpha-fetoprotein (AFP) in these mice. The results of this study suggest that CYP2R1 and CYP26A1 are important in the differentiation of oval cells into hepatoblast-like cells in the injured liver.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hirose
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukaya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Nozomi
authors.initials: N
authors.lastname: Wakui
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitaoka
authors.forename: Jo
authors.initials: J
authors.lastname: Hatogai
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D015870:Gene Expression; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D011725:Pyridines; D000072516:Retinoic Acid 4-Hydroxylase / Q000235:genetics*
chemical_list: C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; D011725:Pyridines; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; C569548:Cyp2r1 protein, mouse; D053493:Cholestanetriol 26-Monooxygenase