title: [Hepatocyte-specific Pten deficient mice].
abstract: Histological findings of hepatocyte-specific Pten deficient(Pten KO) mice livers were consistent with the criteria of human nonalcoholic steatohepatitis(NASH). Therefore, Pten KO mice are a powerful animal model of NASH. In Pten KO mice livers, steatosis develops based on the increased expression of genes that promote fatty acids synthesis. The increased expression of beta, oxidation-related genes accumulates oxidative stress in Pten KO mice livers resulting in hepatitis based on lipid hyperoxidation of hepatocytes membranes. Onset and exacerbation of hepatitis are also related to endotoxins derived from intestinal bacteria. Oxidative DNA damage, hyperproliferation of hepatocytes induced by the activation of Akt and ERK, and the increasement of malignant potential based on the change of fatty acids composition in the livers contribute to the development of hepatocellular carcinoma in Pten KO mice. Since it is considered that the mechanism to induce hepatic lesions in some NASH patients is the same as that in Pten KO mice, the investigation using Pten KO mice gives us clues to clarify the pathogenesis or develop effective therapy of NASH.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Akita University School of Medicine.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000235:genetics; D008099:Liver / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D005227:Fatty Acids; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse