Involvement of TGF-β1 signaling in cardiomyocyte differentiation from P19CL6 cells

Joong Yeon Lim, Won Ho Kim, Joon Kim, Sang Ick Park

Research output: Contribution to journalArticle

19 Citations (Scopus)

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-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-β1-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.

Original languageEnglish
Pages (from-to)431-436
Number of pages6
JournalMolecules and cells
Volume24
Issue number3
Publication statusPublished - 2007 Dec 31

Keywords

  • Cell differentiation
  • Myocyte
  • Smad
  • Transforming growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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