A sustained elevation in retinoic acid receptor-beta 2 mRNA and protein occurs during retinoic acid-induced fetal dysmorphogenesis.
A sustained elevation in retinoic acid receptor-beta 2 mRNA and protein occurs during retinoic acid-induced fetal dysmorphogenesis.
复制标题
在视黄酸诱导的胎儿畸形发生过程中，视黄酸受体-β2 mRNA 和蛋白质持续升高。
DOI：
10.1016/0925-4773(94)90011-6
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发表时间：
1994
影响因子：
2.6
通讯作者：
Kochhar,DM
中科院分区：
文献类型：
--
作者：
Soprano,DR;Gyda3rd,M;Jiang,H;Harnish,DC;Ugen,K;Satre,M;Chen,L;Soprano,KJ;Kochhar,DM
我们之前已经证明，对怀孕小鼠口服全反式维甲酸（RA），其剂量可引起 100% 胎儿畸形发生，导致易感胚胎区域中 RA 受体-β 的一种特定亚型（RAR-β2）的 mRNA 迅速升高。为了进一步研究 RAR-β2 mRNA 在致畸中的作用，我们检查了其在暴露于 13-顺式 RA 和全反式 RA 边缘/非致畸和致畸剂量方案的小鼠胚胎中的表达。我们发现，仅胚胎 RAR-β2 mRNA 水平和游离视黄醇水平的升高不足以导致畸形发生。相反，只有当 RAR-β2 mRNA 和未结合的类视黄醇水平在类视黄醇治疗后至少 6-9 小时保持升高状态，导致 RAR-β 蛋白水平显着且长期升高时，才会发生类视黄醇诱导的胚胎畸形发生。
We have previously shown that oral treatment of pregnant mice with all-transretinoic acid (RA) at doses which cause 100% fetal dysmorphogenesis results in a rapid elevation in the mRNA of one specific isoform of the RA receptor-β, RAR-β2, in susceptible embryonic regions. To further investigate the involvement of RAR-β2 mRNA in teratogenesis, we have examined its expression in mouse embryos exposed to marginal/nonteratogenic and teratogenic dosing regimens of both 13-cisRA and all-transRA. We have found that the mere elevation in embryonic RAR-β2 mRNA levels and free retinoid levels is not sufficient to result in dysmorphogenesis. Rather, retinoid-induced dysmorphogenesis of embryos appears to occur only when RAR-β2 mRNA and unbound retinoid levels remain elevated for at least 6–9 h following retinoid treatment resulting in a significant and prolonged elevation in RAR-β protein levels.