DIFFERENTIATION OF EMBRYONAL CARCINOMA-CELLS TO A NEURAL OR CARDIOMYOCYTE LINEAGE IS ASSOCIATED WITH SELECTIVE EXPRESSION OF ENDOTHELIN RECEPTORS
DIFFERENTIATION OF EMBRYONAL CARCINOMA-CELLS TO A NEURAL OR CARDIOMYOCYTE LINEAGE IS ASSOCIATED WITH SELECTIVE EXPRESSION OF ENDOTHELIN RECEPTORS
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DOI：
10.1074/jbc.270.25.15385
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发表时间：
1995-06-23
影响因子：
4.8
通讯作者：
CERNACEK, P
中科院分区：
文献类型：
--
作者：
MONGE, JC;STEWART, DJ;CERNACEK, P
内皮素（endothelin，ET）最初被认为是一种强有力的血管活性肽，通过至少两种不同的受体ET（A）和ET（B）发挥作用。随后，它们在心脏和其他细胞中的显著生长和肥大促进特性被认识到。我们研究了内皮素受体在多能胚胎癌细胞系（P19）分化为心肌细胞或神经细胞系过程中的表达。这些细胞类似于胚泡的内细胞团的细胞，并且它们的分化被认为与早期胚胎发生中的关键事件非常相似。通过放射性配体结合研究、北方印迹和报告基因分析证实，通过聚集和暴露于二甲基亚砜，P19分化为心肌细胞谱系导致ET（A）受体的诱导。此外，分化为心脏谱系的P19响应于ET-1，心房利钠肽的分泌增加3倍。相反，通过聚集和暴露于视黄酸而分化为神经谱系与主要ET（B）的诱导相关。因此，P19的选择性分化导致内皮素受体的差异表达，其模式与在正常心肌和神经组织中观察到的一致。在早期胚胎发生的模型系统中内皮素受体的诱导为该肽/受体家族在分化和发育中的关键作用提供了强有力的支持。同样，该模型系统非常适合于研究分化过程中控制内皮素受体表达的机制。
Endothelins (ETs) were initially characterized as potent vasoactive peptides acting through at least two distinct receptors, ET(A) and ET(B). Subsequently, their significant growth- and hypertrophy-promoting properties in cardiac and other cells were recognized. We investigated the expression of endothelin receptors during differentiation of a pluripotential embryonal carcinoma cell line (P19) to a cardiomyocyte or a neural lineage. These cells resemble those of the inner cell mass of the blastocyst, and their differentiation is believed to closely mimic critical events in early embryogenesis. Differentiation of P19 to a cardiomyocyte lineage, by aggregation and exposure to dimethyl sulfoxide resulted in induction of ET(A) receptors as demonstrated by radioligand binding studies, Northern blotting, and reporter gene analysis. Moreover, the P19 differentiated to a cardiac lineage responded to ET-1 with a 3-fold increase in the secretion of atrial natriuretic peptide. In contrast, differentiation to a neural lineage, by aggregation and exposure to retinoic acid, was associated with the induction of predominantly ET(B). Therefore, selective differentiation of the P19 led to the differential expression of endothelin receptors in a pattern consistent with that observed in normal myocardial and neural tissue. The induction of endothelin receptors in a model system of early embryogenesis provides strong support for the critical role of this peptide/receptor family in differentiation and development. As well, this model system is well suited for the study of the mechanisms controlling endothelin receptor expression during differentiation.