title: Effect of nuclear receptor downregulation on hepatic expression of cytochrome P450 and transporters in chronic hepatitis C in association with fibrosis development.
abstract: Analysis of mRNAs from liver biopsy samples of patients with chronic hepatitis C revealed that the levels of nuclear receptor expression were correlated with those of drug-metabolizing enzymes and transporters in relation to the development of fibrosis. Overall, the median mRNA level was largely dependent on fibrosis stage (F), and that for stage 3 patients (F3) was about 50% less than that for F1 patients. Levels of expression of AhR, together with CAR and PXR, were lowest in livers of F3 patients. Multivariate linear regression analysis revealed that AhR expression appeared to be involved in the regulation of CYP1A2, 2E1, 2D6, UGT1A, MDR1/3, MRP2/3, NTCP and OCT1 in the livers of patients with chronic hepatitis C. These results suggest that downregulation of AhR during the progression of liver fibrosis is associated with decreased expression levels of these phase I and II enzymes and drug transporters during inflammation-related signal transduction between AhR and other nuclear receptors.
authors.affiliation: Department of Biopharmaceutics, Meiji Pharmaceutical University, Kiyose, Japan. hanada@my-pharm.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hanada
authors.forename: Kenya
authors.initials: K
authors.lastname: Nakai
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogata
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D002467:Cell Nucleus / Q000378:metabolism*; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D051792:Basic Helix-Loop-Helix Proteins; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D029363:Organic Anion Transporters, Sodium-Dependent; D027702:Organic Cation Transporter 1; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D027981:Symporters; C111235:AHR protein, human; C071908:sodium-bile acid cotransporter