Department of Obstetrics and Gynecology, University of Illinois at Chicago, IL 60612, USA.
Biol Reprod. 2010 Jun;82(6):1112-8. doi: 10.1095/biolreprod.109.081844. Epub 2010 Feb 17.
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.
转录共激活因子含有 PDZ 结合基序（TAZ），已知其可与多种转录因子结合，以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 TAZ 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作用，我们利用了体外人子宫成纤维细胞（HuF）细胞模型。免疫细胞化学数据表明，大部分 TAZ 蛋白定位于细胞核内。用胚胎刺激细胞因子白细胞介素 1β（IL-1β）处理 HuF 细胞，并在甾体激素（雌二醇-17β和醋酸甲羟孕酮）存在的情况下培养 13 天，并未引起 TAZ mRNA 发生任何明显变化，但导致总细胞裂解物中的 TAZ 蛋白显著下降（约 62%）。对细胞质和核提取物的分析表明，总 TAZ 的下降主要是由于核内 TAZ 蛋白水平下降所致。通过染色质免疫沉淀检测到，TAZ 定位于 HuF 细胞蜕膜化标记物胰岛素样生长因子结合蛋白 1（IGFBP1）的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（相对于转录起始位点的-1200 bp 位置）上。免疫组织化学也证实了 TAZ 存在于人子宫内膜组织中。在月经周期的分泌期，特定的 TAZ 染色在基质中特别减少，提示其参与蜕膜化过程以及着床。在早期狒狒妊娠期间，接近着床部位的子宫内膜中 TAZ 蛋白表达仍然很少。总之，目前的证据首次表明 TAZ 蛋白存在于人类子宫组织中，其在体外蜕膜化过程中下调，以及其定位于 IGFBP1 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中。
