Wnt/β-catenin-mediated signaling re-activates proliferation of matured cardiomyocytes

作者：Yong Fan, Beatrice Xuan Ho, Jeremy Kah Sheng Pang, Nicole Min Qian Pek, Jin Hui Hor, Shi‐Yan Ng, Boon-Seng Soh · 发表于：Stem Cell Research & Therapy · 年份：2018 · DOI：10.1186/s13287-018-1086-8 · 被引用次数：80 · 研究领域：Congenital heart defects research、Tissue Engineering and Regenerative Medicine、Cardiac Fibrosis and Remodeling

BACKGROUND: The Wnt/β-catenin signaling pathway plays an important role in the development of second heart field (SHF Isl1+) that gives rise to the anterior heart field (AHF) cardiac progenitor cells (CPCs) for the formation of the right ventricle, outflow tract (OFT), and a portion of the inflow tract (IFT). During early cardiogenesis, these AHF CPCs reside within the pharyngeal mesoderm (PM) that provides a microenvironment for them to receive signals that direct their cell fates. Here, N-cadherin, which is weakly expressed by CPCs, plays a significant role by promoting the adhesion of CPCs within the AHF, regulating β-catenin levels in the cytoplasm to maintain high Wnt signaling and cardioproliferation while also preventing the premature differentiation of CPCs. On the contrary, strong expression of N-cadherin observed throughout matured myocardium is associated with downregulation of Wnt signaling due to β-catenin sequestration at the cell membrane, inhibiting cardioproliferation. As such, upregulation of Wnt signaling pathway to enhance cardiac tissue proliferation in mature cardiomyocytes can be explored as an interesting avenue for regenerative treatment to patients who have suffered from myocardial infarction. METHODS: To investigate if Wnt signaling is able to enhance cellular proliferation of matured cardiomyocytes, we treated cardiomyocytes isolated from adult mouse heart and both murine and human ES cell-derived matured cardiomyocytes with N-cadherin antibody or ...