Human Transcriptional Coactivator with PDZ-Binding Motif (TAZ) Is Downregulated During Decidualization
Human Transcriptional Coactivator with PDZ-Binding Motif (TAZ) Is Downregulated During Decidualization
复制标题
DOI：
10.1095/biolreprod.109.081844
复制
发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Ihnatovych, Ivanna
中科院分区：
文献类型：
--
作者：
Strakova, Zuzana;Reed, Jennifer;Ihnatovych, Ivanna
具有PDZ结合基序的转录辅激活因子（TAZ）与多种转录因子结合，控制细胞分化和器官发育。然而，其在子宫生理学中的作用尚未被描述。为了研究其在成纤维细胞分化为蜕膜细胞（蜕膜化）的独特过程中的调节，我们利用人子宫成纤维细胞（HuF）体外细胞模型。免疫细胞化学结果表明，TAZ蛋白主要定位于细胞核内。在类固醇激素（雌二醇-17 β和醋酸甲羟孕酮）存在下，用胚胎刺激细胞因子白细胞介素1 β处理HuF细胞13天，未引起任何明显的TAZ mRNA变化，但导致总细胞裂解物中TAZ蛋白显著下降（约62%）。细胞质和细胞核提取物的分析表明，总TAZ的下降主要是由细胞核中TAZ蛋白水平的下降引起的。染色质免疫沉淀法检测到TAZ位于HuF细胞中蜕膜化标记胰岛素样生长因子结合蛋白1（IGFBP 1）基因组区域的过氧化物酶体增殖物激活受体反应元件位点（位于相对于转录起始位点的位置-1200 bp）。TAZ也存在于人子宫内膜组织中，如通过免疫组织化学证实的。在月经周期的分泌期，特异性TAZ染色在间质中特别减少，表明其参与了蜕膜化过程以及着床。在狒狒妊娠早期，TAZ蛋白表达在靠近着床部位的子宫内膜中保持最小。总之，目前的证据表明，迄今为止第一次TAZ蛋白在人类子宫道，其在体外蜕膜化过程中下调，其定位在IGFBP 1启动子区域，所有这些都表明其存在于妊娠期间的子宫分化程序。
Transcriptional coactivator with PDZ-binding motif (TAZ) is known to bind to a variety of transcription factors to control cell differentiation and organ development. However, its role in uterine physiology has not yet been described. To study its regulation during the unique process of differentiation of fibroblasts into decidual cells (decidualization), we utilized the human uterine fibroblast (HuF) in vitro cell model. Immunocytochemistry data demonstrated that the majority of the TAZ protein is localized in the nucleus. Treatment of HuF cells with the embryonic stimulus cytokine interleukin 1 beta in the presence of steroid hormones (estradiol-17 beta and medroxyprogesterone acetate) for 13 days did not cause any apparent TAZ mRNA changes but resulted in a significant TAZ protein decline (approximately 62%) in total cell lysates. Analysis of cytosolic and nuclear extracts revealed that the decline of total TAZ was caused primarily by a drop of TAZ protein levels in the nucleus. TAZ was localized on the peroxisome proliferator-activated receptor response element site (located at position -1200 bp relative to the transcription start site) of the genomic region of decidualization marker insulin-like growth factor-binding protein 1 (IGFBP1) in HuF cells as detected by chromatin immunoprecipitation. TAZ is also present in human endometrium tissue as confirmed by immunohistochemistry. During the secretory phase of the menstrual cycle, specific TAZ staining particularly diminishes in the stroma, suggesting its participation during the decidualization process, as well as implantation. During early baboon pregnancy, TAZ protein expression remains minimal in the endometrium close to the implantation site. In summary, the presented evidence shows for the first time to date TAZ protein in the human uterine tract, its downregulation during in vitro decidualization, and its localization on the IGFBP1 promoter region, all of which indicate its presence in the uterine differentiation program during pregnancy.