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Cigarette smoke may be an exacerbation factor in nonalcoholic fatty liver disease via modulation of the PI3K/AKT pathway

1 Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan;
2 Department of Microbiology and Immunology and Department of Genome Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan

Mayuko Ichimura and Satoru Matsuda contributed equally to this work.

Special Issues: Gene x Environment Interactions and Systems Biology in Chronic Disease

Nonalcoholic fatty liver disease (NAFLD) characterizes a wide spectrum of pathological abnormalities ranging from simple hepatic steatosis to nonalcoholic steato-hepatitis (NASH). NAFLD may be associated with obesity and the metabolic syndrome. Metabolic syndrome is characterized by hyperglycemia and hyperinsulinemia and also contributes to NASH-associated liver fibrosis. In addition, the presence of reactive oxygen species (ROS), produced by metabolism in normal cells, is one of the most important events in both liver injury and fibrogenesis. Smoking is one of the most common reasons that ROS are produced in a cell. Accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a key molecular event associated with metabolic dysfunction, including NAFLD. Subsequent hepatic stellate cell (HSC) activation is the central event during the diseases. We review recent studies on the features of the PI3K/AKT pathway and discuss the functions in the signaling pathways involved in NAFLD. The molecular mechanisms contributing to the diseases are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies and effective preventions.
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Keywords NAFLD; NASH; PI3K; AKT; PTEN; cell signaling; cigarette; tobacco

Citation: Mayuko Ichimura, Akari Minami, Noriko Nakano, Yasuko Kitagishi, Toshiyuki Murai, Satoru Matsuda. Cigarette smoke may be an exacerbation factor in nonalcoholic fatty liver disease via modulation of the PI3K/AKT pathway. AIMS Molecular Science, 2015, 2(4): 427-439. doi: 10.3934/molsci.2015.4.427


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