经典Wnt 信号通路在心脏瓣膜发育中的作用

心脏瓣膜的形成是脊椎动物心脏发育过程中的重要环节。心脏瓣膜的发育异常会导致心功能不全,是人类先天性心脏病的常见表征之一。经典Wnt 信号通路在心脏发育的不同时期分别作用于心肌细胞、心内皮细胞以及瓣膜原基细胞的增殖、分化和迁移过程,并调控心内膜垫形成过程中的内皮-间充质细胞转化(EndMT)过程,具有多面性和时效性。该文将总结经典Wnt 信号通路在心脏瓣膜发育领域的最新研究进展,分别阐述经典Wnt 信号通路在不同瓣膜发育阶段中的功能变化,并展示经典Wnt 信号通路与其他瓣膜发育相关的信号通路及表观遗传修饰间的相互关系,最后分析心脏发育后期Wnt 信号通路对瓣膜间充质干细胞发挥潜在功能的作用。

Role of the canonical Wnt signaling pathway in heart valve development

Formation of the heart valves is one of critical steps in vertebrate cardiac development. Valvular heart anomaly can induce severe cardiac impairment, which is one of most common symptoms for congenital heart defects (CHD). The canonical Wnt/β-catenin signaling pathway, which is essential for numerous developmental processes, has also been suggested to be involved in the regulation of proliferation, differentiation, and migration of myocardium, endocardium and valve primordia at different stages. The canonical Wnt signaling also regulates the endocardial-mesenchymal transformation (EMT) process during the endocardial cushion formation. This paper reviews current knowledge about the canonical Wnt signaling pathway in heart valve development, including the functional diversities of Wnt activity in heart valve development at different stages and its interaction with other valve-relevant signaling pathways and the potential role of canonical Wnt activity in heart valve mesenchymal stem cells at the late developmental stage.