Cyclooxygenase-2 expression in hepatocytes protects against liver fibrosis in mice through the regulation of miRNA23a-5p

Resumen del trabajo presentado al EMBO Workshop: "Metabolic disorders and liver cancer", celebrado en Palma de Mallorca (España) del 23 al 26 de abril de 2017.Cyclooxygenase-2 (COX-2) is involved in different liver diseases but little is known about the significance of COX-2 in the development and progression of fibrosis. In the present work, hepatocytespecific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were injected with carbon tetrachloride (CC14) for 9 weeks or subjected to bile duct ligation (BDL) for 21 days to induce liver fibrosis. Different cells types were isolated analyzing the expression of a specific set of rniRNAs implicated in liver fibrosis. Furthermore, considering COX-2 expression in hepatocytes could protect against fibrosis by modulating the activation of hepatic stellate cells (HSC), we evaluated the effect of conditioned medium from isolated hepatocytes of COX-2 in primary HSC cells. Our results provide evidence that COX-2-dependent PGs protects against fibrosis by decreasing the Jevels of pro-fibrogenic markers a-SMA and collagen l a l and increasing apoptosis of HSC. Furthermore, the constitutive expression of COX-2 in hepatocytes represses rniRNA-23a-5p expression in HSC cells. These results suggest a protective effect exerted by COX-2 in the process of liver fibrosis, possibly through the downregulation of rniR-23a-5p. Further work is in progress to clarify the role of this miRNA and to identify putative target genes.Peer Reviewe