title: Alteration of the microRNA-122 regulatory network in rat models of hepatotoxicity.
abstract: MicroRNAs are small RNA molecules that post-transcriptionally regulate gene expression. MicroRNA-122 is the most abundant and specific liver microRNA. Hepatotoxicity involves a significant alteration of liver gene expression. The aim of this work was to evaluate the microRNA-122 regulatory network in models of hepatotoxicity induced by thioacetamide or carbon tetrachloride. We report that the toxins decreased the expression of microRNA-122, which corresponded with an increase in two target genes: Cyclin G1 and the cationic amino acid transporter CAT-1. We found a decreased expression of its precursor, pri-microRNA-122, and of the transcription factors that specifically bind its promoter: CCAAT/enhancer-binding protein alpha, and members of the hepatocyte nuclear factor family. Therefore, microRNA-122 expression levels are under transcriptional control during hepatotoxicity. We propose that the changes observed are associated with the liver response to cope with the injury caused by the hepatotoxins, likely through a cell proliferation process to repair the damaged tissue.
authors.affiliation: IFISE, CONICET-UNR, Rosario, S2002LRL, Argentina. Electronic address: lardizabal@ifise-conicet.gov.ar.
authors.forename: María Noelia
authors.initials: MN
authors.lastname: Lardizábal
authors.affiliation: IBR, CONICET-UNR, Rosario, S2002LRL, Argentina. Electronic address: rrodriguez@ibr-conicet.gov.ar.
authors.forename: Ramiro Esteban
authors.initials: RE
authors.lastname: Rodríguez
authors.affiliation: Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, S2002LRL, Argentina. Electronic address: alnocito@gmail.com.
authors.forename: Ana Lía
authors.initials: AL
authors.lastname: Nocito
authors.affiliation: Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, S2002LRL, Argentina. Electronic address: stelladaniele@arnet.com.ar.
authors.forename: Stella Maris
authors.initials: SM
authors.lastname: Daniele
authors.affiliation: IBR, CONICET-UNR, Rosario, S2002LRL, Argentina. Electronic address: palatnik@ibr.gov.ar.
authors.forename: Javier Fernando
authors.initials: JF
authors.lastname: Palatnik
authors.affiliation: IFISE, CONICET-UNR, Rosario, S2002LRL, Argentina; Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, S2002LRL, Argentina. Electronic address: veggi@ifise-conicet.gov.ar.
authors.forename: Luis María
authors.initials: LM
authors.lastname: Veggi
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002251:Carbon Tetrachloride; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D056766:Cyclin G1 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004195:Disease Models, Animal; D005974:Glutamate-Ammonia Ligase / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D014158:Transcription, Genetic
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D027201:Cationic Amino Acid Transporter 1; C530106:Ccnd1 protein, rat; C534704:Ccng1 protein, rat; D056766:Cyclin G1; D051557:Hepatocyte Nuclear Factor 4; C496594:Hnf4a protein, rat; C580643:MIRN122 microRNA, rat; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D013853:Thioacetamide; D019938:Cyclin D1; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D005974:Glutamate-Ammonia Ligase
keywords: CCAAT/enhancer-binding protein alpha; Carbon tetrachloride; Hepatocyte nuclear factor; Hepatotoxicity; Thioacetamide; microRNA-122