ALTERATION OF THE MICRORNA-122 REGULATORY NETWORK IN RAT MODELS OF HEPATOTOXICITY

LARDIZÁBAL, MARIA NOELIA; RODRIGUEZ VIRASORO, RAMIRO ESTEBAN; NOCITO, ANA LÍA; DANIELLE, STELLA MARIS; PALATNIK, JAVIER F; VEGGI, LUIS MARÍA

Chascomús

Jornada; XV Jornadas Anuales de la Sociedad Argentina de Biología; 2013

Sociedad Argentina de Biología

MicroRNAs (miRNAs) are small RNA molecules that post-transcriptionally regulate gene expression. MiRNA-122 is the most abundant and specific liver miRNA. Thioacetamide (TA) and carbon tetrachloride (CT) are two known hepatotoxic widely used as models in rats. The aim of this work was to evaluate the miRNA-122 regulatory network in experimental models of liver damage induced by TA or CT. Adult male Wistar rats received either i.p. TA (150 mg/kg rat), CT (1 ml/kg rat) or vehicles, and were sacrificed 24 hs later. The liver injury was studied by serum ALT levels and histological analysis. MicroRNA and mRNA were measure using RT-qPCR from total RNA purified by Trizol method. We observed that hepatotoxicity decreases miRNA-122 levels and increases the expression of its target genes Cyclin G1 and CAT-1. We also observed a decreased expression of the miRNA-122 precursor (pri-miRNA-122) and of the transcription factors that specifically bind its promoter C/EBP and HNF4Cell proliferation was increased, as indicated by the PCNA and Cyclin D levels. We conclude that miRNA-122 expression levels are under transcriptional control during hepatotoxicity. We propose that this miRNA-122 alteration is 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.