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

被引:16
作者
Radaszkiewicz, Katarzyna Anna [1 ]
Beckerov, Deborah [1 ]
Woloszczukov, Lucie [1 ]
Radaszkiewicz, Tomasz Witold [1 ]
Lesakov, Petra [1 ]
Blanarov, Olga Vondalova [1 ]
Kubala, Lukas [1 ,2 ]
Humpolicek, Petr [3 ,4 ]
Pachernik, Jiri [1 ]
机构
[1] Masaryk Univ, Fac Sci, Dept Expt Biol, Brno, Czech Republic
[2] Acad Sci Czech Republ, Inst Biophys, Dept Free Rad Pathophysiol, Brno, Czech Republic
[3] Tomas Bata Univ Zlin, Ctr Polymer Syst, Zlin 76001, Czech Republic
[4] Tomas Bata Univ Zlin, Fac Technol, Zlin 76001, Czech Republic
关键词
PROTEIN-KINASE-C; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR GATA4; HL-60; CELLS; DIFFERENTIATION; CARDIOMYOCYTES; MESP1; ROLES; IDENTIFICATION; CHELERYTHRINE;
D O I
10.1038/s41598-020-73074-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:13
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