Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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)
  • Received : 2007.03.13
  • Accepted : 2007.06.26
  • Published : 2007.12.31
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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

Acknowledgement

Supported by : Korea National Institute of Health

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