Signaling mechanisms in alcoholic liver injury: Role of transcription factors, kinases and heat shock proteins
Signaling mechanisms in alcoholic liver injury: Role of transcription factors, kinases and heat shock proteins
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DOI：
10.3748/wjg.v13.i37.4979
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发表时间：
2007-10-07
影响因子：
4.3
通讯作者：
Mandrekar, Pranoti
中科院分区：
文献类型：
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作者：
Mandrekar, Pranoti
酒精性肝损伤包括肝脏内多种细胞内信号事件的相互作用。肝脏固有库普弗细胞的先天免疫应答、氧化应激诱导的肝细胞活化、肝星状细胞纤维化事件和肝窦内皮细胞活化都有助于酒精性肝损伤。与酒精性肝损伤相关的信号机制因所涉及的细胞类型和酒精消耗的程度而异。在这篇综述中，我们将阐明酒精对肝细胞氧化应激和信号通路的影响，以及酒精对肝脏库普弗细胞的影响。我们将讨论在酒精诱导炎症中起重要作用的toll样受体及其下游信号事件。酒精诱导肝细胞和巨噬细胞内各种细胞内转录因子（如NF κ B、PPARs和AP-1）以及MAPK激酶的改变，导致肝损伤靶基因的诱导，我们将对此进行综述。最后，我们将讨论热休克蛋白作为伴侣的意义及其在肝脏中的功能调节，这可能为应激诱导的信号机制在酒精性肝损伤中的作用提供新的机制见解。
Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes, fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NF kappa B, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury.