12-O-Tetradecanoylphor bol-13-acetate increases cardiomyogenesis through PKC/ERK signaling

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Authors

RADASZKIEWICZ Katarzyna Anna BECKEROVÁ Deborah WOLOSZCZUKOVÁ Lucie RADASZKIEWICZ Tomasz Witold LESÁKOVÁ Petra VONDÁLOVÁ BLANÁŘOVÁ Olga KUBALA Lukáš HUMPOLÍČEK Petr PACHERNÍK Jiří

Year of publication 2020
Type Article in Periodical
Magazine / Source Scientific reports
MU Faculty or unit

Faculty of Science

Citation
Web https://doi.org/10.1038/s41598-020-73074-4
Doi http://dx.doi.org/10.1038/s41598-020-73074-4
Keywords Cell biology; Developmental biology; Stem cells
Description 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.
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