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Involvement of TGF-β1 Signaling in Cardiomyocyte Differentiation from P19CL6 Cells  

Lim, Joong-Yeon (Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health)
Kim, Won Ho (Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health)
Kim, Joon (Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University)
Park, Sang Ick (Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health)
Publication Information
Molecules and Cells / v.24, no.3, 2007 , pp. 431-436 More about this Journal
Abstract
Stem cell-based therapy is being considered as an alternative treatment for cardiomyopathy. Hence understanding the basic molecular mechanisms of cardiomyocyte differentiation is important. Besides BMP or Wnt family proteins, $TGF-{\beta}$ family members are thought to play a role in cardiac development and differentiation. Although $TGF-{\beta}$ has been reported to induce cardiac differentiation in embryonic stem cells, the differential role of $TGF-{\beta}$ isoforms has not been elucidated. In this study, employing the DMSO-induced cardiomyocyte differentiation system using P19CL6 mouse embryonic teratocarcinoma stem cells, we investigated the $TGF-{\beta}$-induced signaling pathway in cardiomyocyte differentiation. $TGF-{\beta}1$, but not the other two isoforms of $TGF-{\beta}$, was induced at the mRNA and protein level at an early stage of differentiation, and Smad2 phosphorylation increased in parallel with $TGF-{\beta}1$ induction. Inhibition of $TGF-{\beta}1$ activity with $TGF-{\beta}1$-specific neutralizing antibody reduced cell cycle arrest as well as expression of the CDK inhibitor $p21^{WAF1}$. The antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Taken together, these results suggest that $TGF-{\beta}1$ is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.
Keywords
Cell Differentiation; Myocyte; Smad; Transforming Growth Factor;
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Times Cited By Web Of Science : 11  (Related Records In Web of Science)
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