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KMID : 0578320070240030431
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Molecules and Cells
2007 Volume.24 No. 3 p.431 ~ p.436
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Involvement of TGF-β1 Signaling in Cardiomyocyte Differentiation from P19CL6 Cells
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Lim Joong-Yeon
Kim Won-Ho
Kim Joon
Park Sang-Ick
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Abstract
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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-β family members are thought to play a role in cardiac development and differentiation. Although TGF-β has been reported to induce cardiac differentiation in embryonic stem cells, the differential role of TGF-β 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-β-induced signaling pathway in cardiomyocyte differentiation. TGF-β1, but not the other two isoforms of TGF-β, was induced at the mRNA and protein level at an early stage of differentiation, and Smad2 phosphorylation increased in parallel with TGF-β1 induction. Inhibition of TGF-β1 activity with TGF-β 1-specific neutralizing antibody reduced cell cycle arrest as well as expression of the CDK inhibitor p21WAF1. The antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Taken together, these results suggest that TGF-β1 is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.
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KEYWORD
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Cell Differentiation, Myocyte, Smad, Transforming Growth Factor
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