Artículos de revistas
Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice
Fecha
2016-09Registro en:
Motiño, Omar; Agra, Noelia; Brea Contreras, Rocío; Domínguez Moreno, Marina; García Monzón, Carmelo; et al.; Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1862; 9; 9-2016; 1710-1723
0925-4439
CONICET Digital
CONICET
Autor
Motiño, Omar
Agra, Noelia
Brea Contreras, Rocío
Domínguez Moreno, Marina
García Monzón, Carmelo
Vargas Castrillón, Javier
Carnovale, Cristina Ester
Boscá, Lisardo
Casado, Marta
Mayoral, Rafael
Valdecantos, M. Pilar
Valverde, Ángela M.
Frances, Daniel Eleazar Antonio
Martin Sanz, Paloma
Resumen
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 non-alcoholic steatohepatitis (NASH). This study was designed to elucidate the role of COX-2 expression in hepatocytes in the pathogenesis of steatohepatitis and hepatic fibrosis. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were either fed methionine-and-choline deficient (MCD) diet to establish an experimental non-alcoholic steatohepatitis (NASH) model or injected with carbon tetrachloride (CCl4) to induce liver fibrosis. In our animal model, hCOX-2-Tg mice fed MCD diet showed lower grades of steatosis, ballooning and inflammation than Wt mice, in part by reduced recruitment and infiltration of hepatic macrophages, with a corresponding decrease in serum levels of pro-inflammatory cytokines. Furthermore, hCOX-2-Tg mice showed a significant attenuation of the MCD diet-induced increase in oxidative stress and hepatic apoptosis observed in Wt mice. Even more, hCOX-2-Tg mice treated with CCl4 had significantly lower stages of fibrosis and less hepatic content of collagen, hydroxyproline and pro-fibrogenic markers than Wt controls. Collectively, our data indicates that constitutive hepatocyte COX-2 expression ameliorates NASH and liver fibrosis development in mice by reducing inflammation, oxidative stress and apoptosis and by modulating activation of hepatic stellate cells, respectively, suggesting a possible protective role for COX-2 induction in NASH/NAFLD progression.