title: Effect of Trichostatin A on miRNA expression in cultures of primary rat hepatocytes.
abstract: In the present study, the effect of Trichostatin A (TSA), a histone deacetylase inhibitor, was investigated on the microRNA (miR, miRNA) expression profile in cultured primary rat hepatocytes by means of microarray analysis. Simultaneously, albumin secretory capacity and morphological features of the hepatocytes were evaluated throughout the culture time. In total, 25 out of 348 miRNAs were found to be differentially expressed between freshly isolated hepatocytes and 7-day cultured cells. Nineteen of these miRNAs were connected with 'general metabolism'. miR-21 and miR-126 were shown to be the most up and down regulated miRs upon cultivation and could be linked to the proliferative response triggered in the hepatocytes upon their isolation from the liver. miR-379 and miR-143, on the other hand, were found to be the most up and down regulated miRs upon TSA treatment. Together with the higher expression of miR-122 observed in TSA-treated versus non-treated cultures, we hypothesize that the changes observed for miR-122, miR-143 and miR-379 could be related to the inhibitory effects of TSA on hepatocellular proliferation.
authors.affiliation: Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium. jbolleyn@vub.ac.be
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bolleyn
authors.forename: Joanna
authors.initials: J
authors.lastname: Fraczek
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.forename: Daneida
authors.initials: D
authors.lastname: Lizarraga
authors.forename: Stan
authors.initials: S
authors.lastname: Gaj
authors.forename: Joost H M
authors.initials: JH
authors.lastname: van Delft
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015536:Down-Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000633:toxicity*; D006877:Hydroxamic Acids / Q000633:toxicity*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D035683:MicroRNAs; C012589:trichostatin A