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

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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.