Convergence of cAMP, TGF-beta and retinoic acid signaling pathways in cells of the embryonic palate.
Convergence of cAMP, TGF-beta and retinoic acid signaling pathways in cells of the embryonic palate.
复制标题
胚胎腭细胞中 cAMP、TGF-β 和视黄酸信号通路的汇聚。
DOI：
10.1016/s0024-3205(01)01289-9
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发表时间：
2001
期刊：
影响因子：
6.1
通讯作者：
Greene,RM
中科院分区：
文献类型：
--
作者：
Nugent,P;Kusek,JC;Pisano,MM;Greene,RM
我们先前已经描述了在小鼠胚胎腭间充质细胞（MEPM）的原代培养物中视黄酸（RA）和转化生长因子β（TGF-β）信号转导通路之间的双向串扰。本论文研究了TGF-β1、环腺苷酸（cAMP）和RA信号系统之间的相互作用。TGF-β1和forskolin（cAMP途径的激活剂）抑制RA诱导的MEPM细胞RAR-β mRNA的表达，但只有TGF-β1抑制RA诱导的RAR-β蛋白的表达。Forskolin而不是TGF-β1，消除了RA诱导的含有900个碱基对（bp）RAR-β基因启动子的报告构建体的表达，所述报告构建体转染到MEPM细胞中，表明启动子的这一部分含有Forskolin响应性元件，而不是TGF-β响应性元件。因此，RAR-β启动子中与视黄酸反应元件（RARE）相邻的推定TGF-β抑制元件（TIE）是非功能性的，或者需要在这些实验中使用的启动子构建体中不存在的启动子/增强子元件。这些研究进一步阐明了维甲酸受体基因表达调控中信号转导通路之间的复杂相互作用。
We have previously described bi-directional cross-talk between the retinoic acid (RA) and transforming growth factor beta (TGF-β) signal transduction pathways in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. In this paper we identify interactions between the TGF-β1, cyclic adenosine 3′, 5′-monophosphate (cAMP) and RA signaling systems. TGF-β1 and forskolin, an activator of the cAMP pathway, inhibited RA-induced expression of RAR-β mRNA in MEPM cells, though only TGF-β1 inhibited RA-induced RAR-β protein expression. Forskolin, but not TGF-β1, abrogated RA-induced expression of a reporter construct containing 900 base pair (bp) of the RAR-β gene promoter, transfected into MEPM cells, suggesting that this portion of the promoter contains the forskolin-responsive, but not the TGF-β-responsive, element. Thus, a putative TGF-β Inhibitory Element (TIE) adjacent to the retinoic acid response element (RARE) in the RAR-β promoter is either non-functional, or requires promoter/enhancer elements not present in the promoter construct used in these experiments. These studies further clarify the complex interactions among signal transduction pathways in the regulation of retinoic acid receptor gene expression.