Small molecule regulators of postnatal Nkx2.5 cardiomyoblast proliferation and differentiation

Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Journal of Cellular and Molecular Medicine (Impact Factor: 4.01). 12/2011; 16(5):961-5. DOI: 10.1111/j.1582-4934.2011.01513.x
Source: PubMed


While recent data have supported the capacity for a neonatal heart to undergo cardiomyogenesis, it is unclear whether these new cardiomyocytes arise from an immature cardiomyoblast population or from the division of mature cardiomyocytes. By following the expression of enhanced Green Fluorescent Protein (eGFP) in an Nkx2.5 enhancer-eGFP transgenic mice, we have identified a population of immature cells that can undergo cardiomyogenic as well as smooth muscle cell differentiation in the neonatal heart. Here, we examined growth factors and small molecule regulators that potentially regulate the proliferation and cardiomyogenic versus smooth muscle cell differentiation of neonatal Nkx2.5-GFP (+) cells in vitro. We found that A83-01 (A83), an inhibitor of TGF-βRI, was able to induce an expansion of neonatal Nkx2.5-eGFP (+) cells. In addition, the ability of A83 to expand eGFP (+) cells in culture was dependent on signalling from the mitogen-activated protein kinase kinase (MEK) as treatment with a MEK inhibitor, PD0325901, abolished this effect. On the other hand, activation of neonatal Nkx2.5-eGFP (+) cells with TGF-β1, but not activin A nor BMP2, led to smooth muscle cell differentiation, an effect that can be reversed by treatment with A83. In summary, small molecule inhibition of TGF-β signalling may be a promising strategy to induce the expansion of a rare population of postnatal cardiomyoblasts.

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Available from: Sean M Wu, Oct 02, 2015
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    • "Conversely, a recent report shows that left ventricular tissue from fetal HLHS patients, which experiences decreased stretch, has increased expression and activation of Tgf-β1 [16]. Indeed, data from stem cell experiment provide evidence that activated Tgf-β signaling inhibits cardiomyogenesis [22] [23] [24]. Furthermore, data from cultured neonatal rat cardiomyocytes suggest that Tgf-β signaling inhibits cardiomyocyte proliferation in vitro [25] [26]. "
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