Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Genes (Basel). 2020 Sep 30;11(10):1163. doi: 10.3390/genes11101163.
The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.
经典的 Wnt（Wnt/β-catenin）信号通路高度保守，在发育过程中以及成年组织稳态中调节细胞过程中发挥着关键作用。Wnt/β-catenin 信号通路对于正确的身体模式形成至关重要，并参与肠道管（肝脏的原始前体）的命运特化。在成年人中，Wnt/β-catenin 途径越来越被认为是对整个肝脏损伤后代谢分区、稳态更新和再生的重要调节者。在此，我们回顾了该途径在肝脏的模式形成和命运特化、多能干细胞向肝细胞的定向分化以及在成年肝脏中的增殖和分区中的关键作用的最新进展。我们特别关注了最近对损伤后稳态更新和增殖争议的贡献。此外，我们讨论了 Wnt/β-catenin 和 Hedgehog（Hh）以及缺氧诱导因子（HIF）途径之间的串扰如何维持肝脏稳态。深入了解该途径将有助于我们模拟疾病、筛选药物以及为再生医学生成组织和器官替代品。
