Activation of MEK–ERK by heregulin-β1 promotes the development of cardiomyocytes derived from ES cells
- 作者：Hoe Suk Kim ; Jin Won Cho ; Kyoko Hidaka ; Takayuki Morisaki
- 关键词：Embryonic stem cell (ES) cell ; Nkx2.5 transcription factor ; Heregulin-beta1 (HRG-β ; 1) ; Cardiomyocyte ; Extracellular signal-regulated protein kinase (ERK) ; Mitogen-activated protein (MAP) kinase kinase (MEK)
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：28 September 2007
- 卷：361
- 期：3
- 页码：732-738
- 文件大小：478 K
摘要
We have previously shown that heregulin-beta1 (HRG-β1) was involved in the development and survival of cardiomyocytes derived from embryonic stem (ES) cells. This study was conducted to investigate the intracellular signal mechanisms by which HRG-β1 stimulates cardiogenesis in ES cells. The treatment with ErbB receptor inhibitor decreased the population of cardiomyocytes and transcripts levels of cardiac genes (Nkx2.5, β-MHC, cTnI, and MLC2a). The phosphorylation of ERK and development of cardiomyocytes by treatment with HRG-β1 was suppressed upon treatment with MEK1 inhibitor. Furthermore, cardiomyocytes and level of MHC protein were significantly increased by overexpression of wild type MEK1 or constitutive active MEK1, but not dominant negative MEK1. These results suggest that HRG-β1 promotes the development of cardiomyocytes predominantly by activation of MEK–ERK.