Role of Wnt signaling in cardiomyocyte differentiation and its implication for the treatment of heart diseases

随着心脏病患者数量的不断增加，阐明心脏病的病理生理学和开发新的治疗策略势在必行。Wnt信号通路在发育和疾病中发挥着多种作用，最近的研究也发现Wnt信号通路在胚胎期心脏发育和成人心脏病中都有作用。在本研究中，我们阐明了IGFBP4抑制Wnt信号并促进心脏发育的分子机制。我们还发现，激活Wnt信号，然后用小分子抑制Wnt信号，可以有效地诱导人类iPS细胞和小鼠间充质干细胞的心脏分化。最后，我们发现补体蛋白C1q在心力衰竭模型小鼠血清中升高，可能在心力衰竭的进展中起不利作用。

Patients with heart diseases are increasing in number, and elucidation of the pathophysiology and development of novel therapeutic strategies for heart diseases are mandatory. Wnt signaling pathway plays multiple roles in development and diseases, and recent studies have also implicated Wnt signaling both in heart development during embryogenesis and heart diseases in the adult. In the present study, we have clarified the molecular mechanism how IGFBP4 inhibits Wnt signaling and promotes heart development. We have also identified that activation of Wnt signaling followed by inhibition of Wnt signaling by using small molecules can efficiently induce cardiac differentiation of human iPS cells and mouse mesenchymal stem cells. Finally, we have identified that complement protein C1q is increased in the serum of heart failure model mice and may play detrimental role in the progression of heart failure.