During cardiac muscle development, most cardiomyocytes permanently withdraw from the cell cycle. Previously, by suppressive subtractive hybridization, we identified calcyclin-binding protein/Siah-interacting protein (CacyBP/SIP) as one of the candidates being upregulated in the hyperplastic to hypertrophic switch, suggesting an important role of CacyBP/SIP in cardiac development. To show the importance of CacyBP/SIP during myoblast differentiation, we report here that CacyBP/SIP is developmentally regulated in postnatal rat hearts. The overexpression of CacyBP/SIP promotes the differentiation and DNA synthesis of H9C2 cells and primary rat cardiomyocytes, as well as downregulates the expression of beta-catenin. Besides, CacyBP/SIP promotes the formation of myotubes and multinucleation upon differentiation. To investigate the cardioprotective role of CacyBP/SIP in cardiomyocytes, a hypoxia/reoxygenation model was employed. We found that CacyBP/SIP was upregulated during myocardial infarction (MI) and hypoxia/reoxygenation. As a conclusion, CacyBP/SIP may play a role in cardiomyogenic differentiation and possibly protection of cardiomyocytes during hypoxia/reoxygenation injury.

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Cardiovascular diseases have been one of the leading killers among the human population worldwide. During the heart development, cardiomyocytes undergo a transition from hyperplastic to hypertrophic growth with an unclear underlying mechanism. In this study, we aim to investigate how interferons differentially stimulate the interferon-inducible transmembrane (IFITM) family proteins and further be involved in the process of heart development. The expression levels of three IFITM family members, IFITM1, IFITM2, and IFITM3 were investigated during Sprague-Dawley rat myocardial development and differentiation of H9C2 cardiomyocytes. The effects of interferon-α, -β, and -γ on DNA synthesis in H9C2 cells were also characterized. Up-regulation of IFITM1 and IFITM3 were observed during the heart development of Sprague-Dawley rat and the differentiation of H9C2 cells. Moreover, interferon-α and -β induce the expression of IFITM3 while interferon-γ up-regulates IFITM1. Finally, interferon-α and -β were demonstrated to inhibit DNA synthesis during H9C2 cell differentiation. Our results indicated interferons are potentially involved in the differentiation and cell proliferation during heart development.

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