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Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes

机译：Hsp25和p38 MAPK通路参与心肌细胞的分化

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The small heat-shock protein HSP25 is expressed in the heart early during development, and although multiple roles for HSP25 have been proposed, its specific role during development and differentiation is not known. P19 is an embryonal carcinoma cell line which can be induced to differentiate in vitro into either cardiomyocytes or neurons. We have used P19 to examine the role of HSP25 in differentiation, We found that HSP25 expression is strongly increased in P19 cardiomyocytes. Antisense HSP25 expression reduced the extent of cardiomyocyte differentiation and resulted in reduced expression of cardiac actin and the intermediate filament desmin and reduced level of cardiac mRNAs. Thus, HSP25 is necessary for differentiation of P19 into cardiomyocytes. In contrast, P19 neurons did not express HSP25 and antisense HSP25 expression had no effect on neuronal differentiation. The phosphorylation of HSP25 by the p38/SAPK2 pathway is known to be important for certain of its functions. Inhibition of this pathway by the specific inhibitor SB203580 prevented cardiomyocyte differentiation of P19 cells. In contrast, PD90589, which inhibits the ERK1/2 pathway, had no effect. Surprisingly, cardiogenesis was only sensitive to SB203580 during the first 2 days of differentiation, before HSP25 expression increases. In contrast to the effect of antisense HSP25, SB203580 reduced the level of expression of the mesodermal marker Brachyury-T during differentiation. Therefore, we propose that the p38 pathway acts on an essential target during early cardiogenesis. Once this initial step is complete, HSP25 is necessary for the functional differentiation of P19 cardiomyocytes, but its phosphorylation by p38/SAPK2 is not required. (C) 2000 Academic Press. [References: 99]
机译：小的热休克蛋白HSP25在发育早期在心脏中表达，尽管已经提出了HSP25的多种作用，但在发育和分化过程中其具体作用尚不清楚。 P19是一种胚胎癌细胞系，可以在体外诱导分化为心肌细胞或神经元。我们已经使用P19来检查HSP25在分化中的作用。我们发现HSP25在P19心肌细胞中的表达强烈增加。反义HSP25的表达降低了心肌细胞分化的程度，并导致心肌肌动蛋白和中间丝结蛋白的表达降低，以及心肌mRNA的水平降低。因此，HSP25是将P19分化为心肌细胞所必需的。相反，P19神经元不表达HSP25，反义HSP25表达对神经元分化没有影响。已知通过p38 / SAPK2途径使HSP25磷酸化对于其某些功能很重要。通过特异性抑制剂SB203580抑制该途径可防止P19细胞的心肌细胞分化。相反，抑制ERK1 / 2途径的PD90589没有作用。令人惊讶地，在HSP25表达增加之前，心脏分化仅在分化的前2天对SB203580敏感。与反义HSP25的作用相反，SB203580在分化过程中降低了中胚层标记Brachyury-T的表达水平。因此，我们建议p38通路在早期心脏发生过程中作用于一个重要的目标。一旦完成此初始步骤，HSP25对于P19心肌细胞的功能分化是必需的，但不需要通过p38 / SAPK2使其磷酸化。 （C）2000学术出版社。 [参考：99]

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