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Publication : Na+/H+ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation.

First Author  Li X Year  2009
Journal  Am J Physiol Heart Circ Physiol Volume  296
Issue  1 Pages  H159-70
PubMed ID  19011045 Mgi Jnum  J:146335
Mgi Id  MGI:3837281 Doi  10.1152/ajpheart.00375.2008
Citation  Li X, et al. (2009) Na+/H+ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation. Am J Physiol Heart Circ Physiol 296(1):H159-70
abstractText  Embryonic stem cells provide one potential source of cardiomyocytes for cardiac transplantation; however, after differentiation of stem cells in vitro, cardiomyocytes usually account for only a minority of cells present. To gain insights into improving cardiomyocyte development from stem cells, we examined the role of the Na(+)/H(+) exchanger isoform 1 (NHE1) in cardiomyocyte differentiation. NHE1 protein and message levels were induced by treatment of CGR8 cells to form embryoid bodies and cardiomyocytes. The NHE1 protein was present on the cell surface and NHE1 inhibitor-sensitive activity was detected. Inhibition of NHE1 activity during differentiation of CGR8 cells prevented cardiomyocyte differentiation as indicated by decreased message for transcription factors Nkx2-5 and Tbx5 and decreased levels of alpha-myosin heavy chain protein. Increased expression of NHE1 from an adenoviral vector facilitated cardiomyocyte differentiation. Similar results were found with cardiomyocyte differentiation of P19 embryonal carcinoma cells. CGR8 cells were treated to induce differentiation, but when differentiation was inhibited by dispersing the EBs, myocardial development was inhibited. The results demonstrate that NHE1 activity is important in facilitating stem cell differentiation to cardiomyocyte lineage. Elevated NHE1 expression appears to be triggered as part of the process that facilitates cardiomyocyte development.
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