NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma.
NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma.
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DOI：
10.1038/nrgastro.2010.213
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发表时间：
2011-02
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--
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肝硬变和肝细胞癌是慢性肝病患者最常见的死亡原因。几乎任何病因的慢性肝损伤都会触发炎症和伤口愈合反应，从长远来看，这些反应会促进肝纤维化和肝细胞癌的发展。在这里，我们综述了转录因子核因子-κB(NF-κB)在肝细胞损伤、肝纤维化和肝细胞癌发生发展中的作用，尤其是在肝脏不同细胞分区中的作用。我们认为，NF-κB在肝损伤、肝纤维化和肝细胞癌之间起着中心纽带的作用，它可能是预防或治疗肝纤维化和肝细胞癌的靶点。然而，NF-κB是一把双刃剑，抑制NF-κB不仅可以发挥有益的作用，而且还会对肝细胞的活力产生负面影响，特别是当抑制NF-κB时。寻找合适的靶点或确定仅对NF-κB活性产生温和影响或可特异性传递给非实质细胞的药物，对于避免因完全阻断肝细胞中的NF-κB而导致的肝损伤增加至关重要。
Hepatic cirrhosis and hepatocellular carcinoma (HCC) are the most common causes of death in patients with chronic liver disease. Chronic liver injury of virtually any etiology triggers inflammatory and wound healing responses that in the long run promote the development of hepatic fibrosis and HCC. Here, we review the role of the transcription factor nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death, in the development of hepatocellular injury, liver fibrosis and HCC, with a particular focus on the role of NF-κB in different cellular compartments of the liver. We propose that NF-κB acts as a central link between hepatic injury, fibrosis and HCC, and that it may represent a target for the prevention or treatment of liver fibrosis and HCC. However, NF-κB acts as a two-edged sword and inhibition of NF-κB may not only exert beneficial effects but also negatively impact hepatocyte viability, especially when NF-κB inhibition is pronounced. Finding appropriate targets or identifying drugs that either exert only a moderate effect on NFκB activity or that can be specifically delivered to nonparenchymal cells will be essential to avoid the increase in liver injury associated with complete NF-κB blockade in hepatocytes.
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