| Co-Investigator(Kenkyū-buntansha) |
MORISHIMA Masae Tokyo Women's Medical University, Medicine, Research Associate, 医学部, 助手 (00241068)
MIYAGAWA Sachiko Tokyo Women's Medical University, Medicine, Research Associate, 医学部, 助手 (40231451)
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| Research Abstract |
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.
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