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Retinoic acid receptors in mouse hearts during development

小鼠心脏发育过程中的视黄酸受体

基本信息

批准号：
09671199
负责人：
NAKAZAWA Makoto
金额：
$ 2.05万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671199/
关键词：
developing heart retinoic acid retinoic acid receptor mouse embryo TGF-β transcription factor TGF-β 心形態・形成

项目摘要

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.

小鼠胚胎暴露于过量维甲酸（RA）诱导大动脉转位的高频率。RA缺乏，或缺乏维甲酸受体（RAR）或维甲酸X受体-α的转导RA信号也与心血管异常有关。ra依赖基因的功能障碍可能是先天性心脏病病因学的关键因素。我们检测了RAR-α、RAR-β和RAR-γ (LGME-U.184)在正常和ra处理小鼠心肌中的表达。同时观察TGF-β1、TGF-β2、TGF-β3的表达。在RA处理的心脏中，RA处理可诱导RAR-α和RAR-β、TGF-βs RNA在心脏中的表达。然而，当将妊娠第12.5天小鼠胚胎心脏分为心房、心室和流出道三个区域时，这些基因转录对RA的敏感性在每个区域有所不同。在RA处理的心脏流出道中，RAR-γ和TGF-β3 RNA表达上调，RNR-β和TGF-β2表达下调。心房TGF-β1、β2、β3表达上调，RAR-β表达下调。这些结果表明，RAR和TGF-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的敏感性不同。这些数据可能有助于了解大动脉转位的发病机制。