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Mitogen-activated protein kinase in endothelin-1-induced cardiac differentiation of mouse embryonic stem cells.
Chen, Ming; Lin, Yong-Qing; Xie, Shuang-Lun; Wang, Jing-Feng.
Afiliación
  • Chen M; Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
J Cell Biochem ; 111(6): 1619-28, 2010 Dec 15.
Article en En | MEDLINE | ID: mdl-21053276
Endothelin-1(ET-1) is a potent vasoconstrictor involved in the development of cardiovascular diseases and is an important regulator of heart development. However, the role of ET-1 in cardiac differentiation of mouse embryonic stem cells (mESCs) and the underlying molecular mechanisms remain poorly understood. In the present study, we showed that ET-1 significantly up-regulated gene expression of the cardiac specific transcriptional factors Nkx2.5, GATA4, and conduction system specific marker CX40, with no affect on the gene expression of α-MHC and ß-MHC in cardiac differentiation of mESCs. The percentage of beating embryoid bodies (EB) and the Troponin T (TnT) positive area in total EBs was unchanged following ET-1 treatment, while the percentage of spindle cells that stained positively with TnT was increased in the presence of ET-1. Further investigation indicated that the percentage of beating EBs and the TnT positive area were decreased by the extracellular signal-related kinases (ERK)-1/2 inhibitor U0126 and the p38 inhibitor SB203580, but not by the Jun amino-terminal kinases (JNK) inhibitor SP600125. Inhibition of ERK1/2, p38, and JNK pathways also blocked the up-regulation of Nkx2.5 and GATA4 by ET-1, however only inhibition of the ERK1/2 pathway had negatively effects on the increase in CX40 expression in response to ET-1. ET-1 induced an increase in the percentage of spindle cells was also inhibited by U0126. Our results suggest that ET-1 plays a significant role in the cardiac differentiation of mESCs, especially in those cells committed to the conduction system, with the ERK1/2 pathway playing a critical role in this process.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Diferenciación Celular / Endotelina-1 / Proteínas Quinasas Activadas por Mitógenos / Células Madre Embrionarias Límite: Animals Idioma: En Revista: J Cell Biochem Año: 2010 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Diferenciación Celular / Endotelina-1 / Proteínas Quinasas Activadas por Mitógenos / Células Madre Embrionarias Límite: Animals Idioma: En Revista: J Cell Biochem Año: 2010 Tipo del documento: Article País de afiliación: China