Thompson Michael D, Monga Satdarshan P S
Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
Hepatology. 2007 May;45(5):1298-305. doi: 10.1002/hep.21651.
Wnt/beta-catenin signaling is emerging as a forerunner for its critical roles in many facets of human biology. Its roles in embryogenesis, organogenesis, and maintaining tissue and organ homeostasis demonstrate its munificent character. Its roles in pathological conditions such as cancer and other human disorders such as inflammatory disorders and fibrosis reveal its villainous disposition. In liver, it also maintains its dual personality and is clearly of essence in several physiological events such as development, regeneration, and growth. Its aberrant activation is also evident in many different tumors of the liver, and recent studies are beginning to identify its role in additional hepatic pathological conditions. It is contributing to liver physiology and pathology by regulating various basic cellular events, including differentiation, proliferation, survival, oxidative stress, morphogenesis, and others. This review discusses the contribution of the Wnt/beta-catenin signaling pathway in these events and simultaneously provides an essential overview of the major developments in the field of Wnt/beta-catenin and liver pathobiology. In addition, areas that are currently deficient or understudied are identified and discussed along with the avenues of translational and clinical relevance.
Wnt/β-连环蛋白信号通路因其在人类生物学诸多方面的关键作用而崭露头角。它在胚胎发生、器官发生以及维持组织和器官稳态中的作用彰显了其重要性。它在诸如癌症等病理状况以及诸如炎症性疾病和纤维化等其他人类疾病中的作用揭示了其有害的一面。在肝脏中,它同样具有双重特性,并且在诸如发育、再生和生长等若干生理过程中显然至关重要。其异常激活在许多不同的肝脏肿瘤中也很明显,并且最近的研究开始确定其在其他肝脏病理状况中的作用。它通过调节各种基本细胞事件,包括分化、增殖、存活、氧化应激、形态发生等,对肝脏生理和病理产生影响。本综述讨论了Wnt/β-连环蛋白信号通路在这些事件中的作用,同时对Wnt/β-连环蛋白与肝脏病理生物学领域的主要进展进行了必要概述。此外,还确定并讨论了当前存在不足或研究较少的领域以及转化和临床相关性的途径。