title: Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period.
abstract: Previous works have shown that differentiated human HepaRG cells can exhibit drug metabolism activities close to those of primary human hepatocytes for several weeks at confluence. The present study was designed to evaluate their long-term functional stability and their response to repeated daily drug treatments over a 14-day period, using a transcriptomic approach. Our data show that less than 1% of the expressed genes were markedly deregulated over this two weeks period and mainly included down-regulation of genes related to the cell cycle and from 3 days, overexpression of genes involved in xenobiotic and lipid metabolism. After daily treatment with the three PPAR agonists, fenofibrate, troglitazone and rosiglitazone qualitative and/or quantitative changes in gene profiling were observed depending on the compound and duration of treatment. The highest increase in the number of deregulated genes as a function of drug treatment was seen with rosiglitazone. The most up-regulated genes common across the three compounds were mainly related to lipid and xenobiotic metabolisms. All the data support the conclusion that human HepaRG cells have an exceptional functional stability at confluence and that they are suitable for investigations on chronic effects of drugs and other chemicals.
authors.affiliation: Inserm U991, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France; Université de Rennes 1, France.
authors.forename: Camille C
authors.initials: CC
authors.lastname: Savary
authors.affiliation: Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Université de Rennes 1, France; Plate-forme Génomique Santé Biosit, Rennes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Aubry
authors.affiliation: Inserm U991, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France; Université de Rennes 1, France.
authors.forename: Rozenn
authors.initials: R
authors.lastname: Jossé
authors.affiliation: Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Kopp-Schneider
authors.affiliation: Non-Clinical Safety, Merck Serono, Merck KGaA, Darmstadt, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Hewitt
authors.affiliation: Inserm U991, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France; Université de Rennes 1, France. Electronic address: andre.guillouzo@univ-rennes1.fr.
authors.forename: André
authors.initials: A
authors.lastname: Guillouzo
mesh_terms: D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D004334:Drug Administration Schedule; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D046228:Microarray Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D059467:Transcriptome / Q000187:drug effects*; D000077288:Troglitazone
chemical_list: D002839:Chromans; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone; D011345:Fenofibrate
keywords: Gene profiling; HepaRG cells; PPAR agonists; Repeated treatments; Time-dependent changes; Transcriptomics