P19C16 cell line에서 심장근육세포로의 분화에 있어서 TGF-β1 signaling의 관련역할 연구

초록

Purpose : TGF-β family members are known to be involved in cardiac development and cardiomyocyte differentiation. In this study, we asked the functional role of TGF-β1 among the three TGF—β isoforms in cardiomyocyte differentiation. Methods : Employing DMSO-induced cardiomyocyte differentiation system using P19CL6 mouse embryonic teratocarcinoma stem cells, we investigated the TGF-β 1-induced signaling pathway during cardiomyocyte differentiation. Results : Of the three TGF-β isoforms only TGF-β1 was induced at the mRNA and protein level at an early stage of differentiation. Smad2 activation(phosphorylation) was increased in parallel with the timing of TGF—β1 induction. Inhibition of TGF-β1 activity with TGF-β1-specific neutralizing antibody reduced cell cycle arrest as well as the expression of CDK inhibitor p21^(WAF1). Additionally, the neutralizing antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Conclusions : In this study our results suggest that TGF-βi is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.

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