Retinoic acid receptors in mouse hearts during development

小鼠胚胎暴露在过量的维甲酸(RA)中会导致大动脉移位的频率很高。RA缺乏或缺乏转导RA信号的维甲酸受体或维甲酸X受体-α也与心血管异常有关。RA依赖基因功能障碍可能是先天性心脏病发病的关键因素之一。我们检测了RAR-α、RAR-β和RAR-γ(LGME-U184)在正常和RA处理的小鼠胚胎心脏中的表达。同时观察转化生长因子-β-1、转化生长因子-β-2、转化生长因子-β3的表达。在RA处理的心脏中，RA-α、RAR-β、转化生长因子-β、S的表达被RA-1诱导。然而，当妊娠12.5天的小鼠胚胎心脏被分成三个区域：心房、心室和流出道时，这些基因转录在每个区域对RA的敏感性不同。在RA处理的心脏流出道中，RAR-γ和转化生长因子-β-3RNA表达上调，RNR-β和转化生长因子-β-2表达下调。在心脏心房，转化生长因子-β1、β-2和β-3表达上调，RAR-β表达下调。这些结果表明，RAR和转化生长因子-β基因在适当的时间表达，以影响心脏发育的不同方面，并且胚胎心脏的每个区域对RA具有不同的敏感性。这些数据可能有助于了解大动脉转位的发病机制。

Exposure of mouse embryos to excess retinoic acid (RA) induces a high frequency of transposition of the great arteries. RA deficiency, or lack of retinoic acid receptors (RAR) or retinoid X receptor-α which transduce the RA signal are also associated with cardiovascular anomalies. Dysfunction of RA-dependent genes may be a key element in the etiology of congenital heart disease. We examined the expression of RAR-α, RAR-β and RAR-γ (LGME-U.184) in normal and RA-treated mouse embroynic hearts. We also looked at TGF-β1, TGF-β2, TGF-β3 expression simultaneously. In RA-treated hearts, the expression of RAR-α and RAR-β, TGF-βs RNA in the hearts was induced by RA, treatment. However, the sensitivity of those gene transcriptions to RA was different in each region when mouse embryonic hearts at gestation day 12.5 were divided to three gegions : atrium, ventricle and outflow tract. In the outflow tract of the heart treated with RA, the expression of RAR-γ and TGF-β3 RNA was up-regulated and expression of RNR-β and TGF-β2 was down-regulated. In the atrium of the heart the expression of TGF-β1, β2, and β3 was up-regulated and expression of RAR-β was down-regulated. These results suggest that RAR and TGF-β genes are expressed at times appropriate to influence different aspects of heart development, and each region of the embryonic heart has a different sensitivity to RA. These data might be helpful for understanding the pathogenesis of transposition of the great arteries.