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Rôle de l'ostéopontine dans les complications hépatiques induites par l'alcool, l'obésité et l'ischémie-reperfusion

Abstract : Osteopontin (OPN) is a protein synthesized and secreted by many different types of cells. It plays an important part in the regulation of the inflammatory and immune response. OPN is also pro-fibrogenic, and has anti-apoptotic properties. The nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the leading causes of liver disease in France. The range of these complications goes from steatosis to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Adipose tissue plays a significant part on the occurrence and evolution of the NAFLD. We show that OPN facilitates liver’s and adipose tissue’s inflammation in the NAFLD, by facilitating the intake of macrophages, dendritic cells and T cells, and by modulating the polarization of these immune cells. For alcoholic patients, we show that OPN is one of the predictive markers of liver fibrosis. The lesions induced by ischemia-reperfusion (IR) are the main cause of damages occurring during liver’s surgery. The role of OPN in hepatic injury induced by IR has not yet been investigated. My studies demonstrate that OPN could have a protecting role. OPN deficiency in mice (OPN-/-) increases hepatic lesions caused by IR (inflammation, and cell death). OPN could thus partially prevent hepatic injury and inflammation induced by IR. This could be due to its ability to prevent hepatocyte death and production of toxic NO by macrophages. OPN could thus be an important actor in the pathogenesis of chronic liver disease.
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Stéphanie Patouraux. Rôle de l'ostéopontine dans les complications hépatiques induites par l'alcool, l'obésité et l'ischémie-reperfusion. Sciences agricoles. Université Nice Sophia Antipolis, 2014. Français. ⟨NNT : 2014NICE4134⟩. ⟨tel-01249404⟩

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