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Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice

AuthorsMotiño, Omar ; Agra, Noelia ; Brea, Rocío; Domínguez-Moreno, Marina; García-Monzón, Carmelo; Carnovale, Cristina E.; Boscá, Lisardo ; Casado, Marta ; Mayoral, Rafael ; Valdecantos, M. P.; Valverde, Ángela M.; Francés, Daniel E.; Martín-Sanz, Paloma
Issue Date2016
CitationLiver Biology - Fundamental Mechanisms and Translational Applications (2016)
AbstractCyclooxygenase-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 (CC14) 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 mi ce 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 mi ce treated with CC14 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.
DescriptionResumen del póster presentado a la Conferencia Liver Biology - Fundamental Mechanisms and Translational Applications, celebrada en Palm Beach (USA) del 26 de junio al 1 de julio de 2016.
Appears in Collections:(IIBM) Comunicaciones congresos
(IBV) Comunicaciones congresos
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