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.

小鼠胚胎暴露于多余的视黄酸（RA）会引起大动脉换位的高频。 RA缺乏症，或缺乏视黄酸受体（RAR）或类维生素X受体-α（转导RA信号）也与心血管异常有关。 RA依赖性基因功能障碍可能是先天性心脏病病因的关键因素。我们检查了正常和RA处理的小鼠胚胎心脏中RAR-α，RAR-β和RAR-γ（LGME-U.184）的表达。我们还同时研究了TGF-β1，TGF-β2，TGF-β3表达。在RA处理的心脏中，RAR-α和RAR-β的表达，心脏中的TGF-βSRNA是由RA，处理的。然而，当妊娠12.5时小鼠胚胎心脏分为三个地质：中庭，通风和出口大道时，这些基因转录对RA的敏感性在每个区域都不同。在用RA处理的心脏的输出道中，RAR-γ和TGF-β3RNA的表达被上调，RNR-β和TGF-β2的表达下调。在心脏中庭中，TGF-β1，β2和β3的表达被上调，RAR-β的表达下调。这些结果表明，RAR和TGF-β基因有时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都有不同的敏感性。这些数据可能有助于理解大动脉换位的发病机理。