Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells.
Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells.
复制标题
配体激活的松弛素受体可增加人蜕膜和子宫内膜基质细胞中 IGFBP-1 和催乳素的转录。
DOI：
10.1093/molehr/gah149
复制
发表时间：
2005
影响因子：
4
通讯作者：
Tseng,Linda
中科院分区：
文献类型：
--
作者：
Tang,Meiyi;Mazella,James;Zhu,HuiHui;Tseng,Linda
本研究的目的是探讨松弛素（RLX）受体介导的基因激活在人类子宫内膜。我们测定了胰岛素样生长因子结合蛋白-1（IGFBP-1）和催乳素（PRL）的启动子活性，并鉴定了人蜕膜细胞和子宫内膜基质细胞中介导RLX激活转录的序列。在人蜕膜细胞中，IGFBP-1的启动子活性在与RLX孵育的细胞中显著增加。在子宫内膜基质细胞中，RLX介导的活化仅在基质细胞与RLX受体（LGR 7）表达载体共转染时增强，而单独的RLX几乎没有作用（Mazellaet al.，2004年）。缺失和突变分析表明，IGFBP-1启动子中的cAMP调控元件（CRE，−263至−259 bp）对激活至关重要。此外，RLX增加CRE结合蛋白的磷酸化（CREB为p-CREB），p-CREB位于细胞核中，表明RLX激活蜕膜细胞中的蛋白激酶（PKA）系统。凝胶迁移实验表明，从RLX处理蜕膜细胞制备的核提取物增加了IGFBP-1启动子的CRE位点的结合。RLX通过含有多个CCAAT/增强子结合蛋白（C/EBP）结合位点的区域介导的PRL启动子活性增加，所述CCAAT/增强子结合蛋白（C/EBP）结合位点已显示通过cAMP类似物介导PRL基因活化（Pohnkeet al.，1999年）。RLX增强的IGFBP-1启动子活性被cAMP依赖性PKA抑制剂H-89抑制。PRL启动子活性被H-89和U 0126抑制，表明RLX在子宫内膜细胞中激活了多个信号通路，用于不同的靶基因激活。
The aim of this study was to investigate relaxin (RLX) receptor-mediated gene activation in human endometrium. We determined the promoter activities of insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin (PRL) and identified sequence(s) that mediate RLX activated transcription in human decidual cells and endometrial stromal cells. In human decidual cells, the promoter activity of IGFBP-1 was increased significantly in cells incubated with RLX. In endometrial stromal cells, the RLX mediated activation was enhanced only when stromal cells were co-transfected with RLX-receptor (LGR7) expression vector and RLX alone had little effect (Mazellaet al., 2004). Deletion and mutation analysis showed that the cAMP regulatory element (CRE, −263 to −259 bp) in the IGFBP-1 promoter was essential for the activation. In addition, RLX increased the phosphorylation of CRE binding protein (CREB to p-CREB) and p-CREB resided in the nucleus, indicating that RLX activates the protein kinase (PKA) system in decidual cells. Gel shift assay showed that nuclear extracts prepared from RLX treated decidual cells increased the binding to the CRE site of the IGFBP-1 promoter. RLX increased the PRL promoter activity mediated through the region containing multiple CCAAT/enhancer-binding proteins (C/EBP) binding sites that have been shown to mediate the PRL gene activation by cAMP analogue (Pohnkeet al., 1999). RLX enhanced IGFBP-1 promoter activity was inhibited by cAMP dependent PKA inhibitor, H-89. PRL promoter activity was inhibited by both H-89 and U0126 indicating multiple signalling pathways are activated by RLX in endometrial cells for different target gene activation.