Liver Research Group, Institute of Cellular Medicine, 4th Floor, Catherine Cookson Building, Medical School, Newcastle University, UK.
J Hepatol. 2010 Feb;52(2):285-91. doi: 10.1016/j.jhep.2009.10.030. Epub 2009 Nov 24.
NF-kappaB is a dimeric transcription factor that has emerged as an important regulator of liver homeostasis and is mechanistically implicated in a variety of liver pathologies including hepatitis, steatosis, fibrosis, and hepatocellular carcinoma. The question remains as to whether NF-kappaB can really be exploited for the development of therapeutics for these pathologies in the diseased human liver. This review casts a critical eye on the experimental evidence gathered to date and in particular questions the rationale for the current focus on components of the upstream IKK complex as therapeutic targets. We make the argument that translation of NF-kappaB biology to new therapies is more likely to emerge from a re-focus of basic research back to the NF-kappaB/Rel subunit functions and the complexities of their post-translational modifications and context-dependent co-regulator interactions.
NF-κB 是一种二聚体转录因子，已成为肝脏内稳态的重要调节剂，并且在多种肝脏疾病（包括肝炎、脂肪变性、纤维化和肝细胞癌）的发病机制中具有重要作用。问题仍然是 NF-κB 是否真的可以被用于开发治疗这些疾病的药物。本综述批判性地审视了迄今为止收集的实验证据，特别是对目前将上游 IKK 复合物作为治疗靶点的成分作为治疗靶点的合理性提出了质疑。我们认为，将 NF-κB 生物学转化为新的治疗方法更有可能重新关注基本研究，重新关注 NF-κB/Rel 亚基的功能及其翻译后修饰的复杂性和依赖于上下文的共同调节剂相互作用。
