Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease.
Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease.
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DOI：
10.1155/2013/472432
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kitagishi Y
中科院分区：
文献类型：
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作者：
Matsuda S;Kobayashi M;Kitagishi Y
非酒精性脂肪性肝病(NAFLD)是最常见的肝脏病理类型，与肥胖和代谢综合征有关，代谢综合征代表一系列与2型糖尿病风险增加相关的脂肪肝疾病。如何从单纯性脂肪肝转变为非酒精性脂肪性肝炎(NASH)的分子机制尚不清楚。然而，越来越多的证据表明，肝细胞中磷脂酰肌醇3-激酶(PI3K)/AKT通路的失控是一种常见的与代谢功能障碍相关的分子事件，包括肥胖、代谢综合征和NAFLD。抑癌基因PTEN通过其脂磷酸酶活性负性调节PI3K/AKT信号通路。NAFLD的分子研究支持PTEN在肝脏胰岛素敏感性以及脂肪变性、脂肪性肝炎和纤维化的发展中起关键作用。我们综述了近年来PTEN和PI3K/AKT信号转导途径的研究进展，并讨论了蛋白在NAFLD信号转导通路中的功能。导致这些疾病的分子机制是大量研究的主题，因为对发病机制的更好理解将导致对一种疾病的新的治疗方法。
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome, which represents a range of fatty liver diseases associated with an increased risk of type 2 diabetes. Molecular mechanisms underlying how to make transition from simple fatty liver to nonalcoholic steatohepatitis (NASH) are not well understood. However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the 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 for a condition.