12-O-Tetradecanoylphorbol-13-acetate (TPA) is the most widely used diacylglycerol (DAG) mimetic agent and inducer of protein kinase C (PKC)-mediated cellular response in biomedical studies. TPA has been proposed as a pluripotent cell differentiation factor, but results obtained have been inconsistent. In the present study we show that TPA can be applied as a cardiomyogenesis-promoting factor for the differentiation of mouse embryonic stem (mES) cells in vitro. The mechanism of TPA action is mediated by the induction of extracellular signal-regulated kinase (ERK) activity and the subsequent phosphorylation of GATA4 transcription factor. Interestingly, general mitogens (FGF, EGF, VEGF and serum) or canonical WNT signalling did not mimic the effect of TPA. Moreover, on the basis of our results, we postulate that a TPA-sensitive population of cardiac progenitor cells exists at a certain time point (after days 6-8 of the differentiation protocol) and that the proposed treatment can be used to increase the multiplication of ES cell-derived cardiomyocytes.

• MeSH
• Cell Differentiation drug effects   MeSH
• Embryonic Stem Cells cytology   drug effects   metabolism   MeSH
• Extracellular Signal-Regulated MAP Kinases metabolism   MeSH
• Phosphorylation MeSH
• Myocytes, Cardiac cytology   metabolism   MeSH
• Mice MeSH
• Protein Kinase C metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Tetradecanoylphorbol Acetate pharmacology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Extracellular Signal-Regulated MAP Kinases MeSH
• Protein Kinase C MeSH
• Tetradecanoylphorbol Acetate MeSH