Small molecule regulators of postnatal Nkx2.5 cardiomyoblast proliferation and differentiation
Journal
Journal of Cellular and Molecular Medicine
Journal Volume
16
Journal Issue
5
Pages
961-965
Date Issued
2012
Author(s)
Wu S.M.
Abstract
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. ? 2011 The Authors Journal of Cellular and Molecular Medicine ? 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
SDGs
Other Subjects
a 83 01; A-83-01; activin; activin A; benzamide derivative; bone morphogenetic protein 2; diphenylamine; drug derivative; enzyme inhibitor; homeodomain protein; mitogen activated protein kinase kinase; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; Nkx2 5 protein, mouse; Nkx2-5 protein, mouse; protein serine threonine kinase; pyrazole derivative; signal peptide; TGF beta type I receptor; TGF-beta type I receptor; thiocarbamic acid derivative; transcription factor; transforming growth factor beta receptor; transforming growth factor beta1; animal; cell culture; cell proliferation; drug antagonism; drug effect; genetics; human; metabolism; mouse; muscle development; myoblast; physiology; review; transgenic mouse; Activins; Animals; Benzamides; Bone Morphogenetic Protein 2; Cell Proliferation; Cells, Cultured; Diphenylamine; Enzyme Inhibitors; Homeodomain Proteins; Humans; Intercellular Signaling Peptides and Proteins; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase Kinases; Muscle Development; Myoblasts, Cardiac; Protein-Serine-Threonine Kinases; Pyrazoles; Receptors, Transforming Growth Factor beta; Thiocarbamates; Transcription Factors; Transforming Growth Factor beta1; Mus musculus
Type
review