Tyson-Capper Alison J, Cork David M W, Wesley Emily, Shiells Elizabeth A, Loughney Andrew D
School of Surgical and Reproductive Sciences, The Medical School, University of Newcastle upon Tyne, UK.
Mol Hum Reprod. 2006 Nov;12(11):695-701. doi: 10.1093/molehr/gal070. Epub 2006 Sep 7.
Many complementary or competing signalling pathways bear an influence on the myometrium at any one time, and because the retinoic acid signalling pathway influences differentiation of a wide array of human tissues, this may be one of the determinants of myometrial differentiation during pregnancy. We have explored the novel hypothesis that the retinoids may act as important regulators in controlling the differentiated state of the human myometrium during pregnancy by characterizing the expression profiles for cellular retinoid-binding proteins CRBPI, CRABPI and CRABPII in non-pregnant, pregnant (non-labouring) and labouring human myometrium taken from the functionally distinct upper and lower uterine segments. In addition, we have investigated the effect of all-trans retinoic acid (ATRA) on the expression of several retinoic acid response genes including cyclooxygenase-2 (COX-2) and connexin-43 (Cx-43). Different spatial and temporal patterns of expression were observed for CRBPI, CRABPI and CRABPII within the upper and lower uterine segments through the three trimesters of pregnancy and in labour. Furthermore, the expression of COX-2, Cx-43, CRABPI, the transcription factor c-Jun and the retinoic acid receptor RARbeta altered in response to different concentrations of ATRA, suggesting that the differential expression of cellular retinoid-binding proteins may lead to different levels of retinoic acid being delivered to its nuclear targets, leading to the differential expression of specific target genes within the myometrium during pregnancy.
在任何时刻,许多互补或相互竞争的信号通路都会对子宫肌层产生影响。由于视黄酸信号通路会影响多种人体组织的分化,因此这可能是孕期子宫肌层分化的决定因素之一。我们通过对取自功能不同的子宫上段和下段的非孕、妊娠(未临产)和临产人体子宫肌层中细胞视黄酸结合蛋白CRBPI、CRABPI和CRABPII的表达谱进行表征,探讨了一种新的假说,即类视黄醇可能作为重要的调节因子,在孕期控制人体子宫肌层的分化状态。此外,我们还研究了全反式视黄酸(ATRA)对包括环氧合酶-2(COX-2)和连接蛋白-43(Cx-43)在内的几种视黄酸反应基因表达的影响。在孕期的三个阶段以及分娩过程中,子宫上段和下段的CRBPI、CRABPI和CRABPII呈现出不同的时空表达模式。此外,COX-2、Cx-43、CRABPI、转录因子c-Jun和视黄酸受体RARβ的表达会因不同浓度的ATRA而发生改变,这表明细胞视黄酸结合蛋白的差异表达可能导致视黄酸传递至其核靶点的水平不同,进而导致孕期子宫肌层内特定靶基因的差异表达。