Transcription factor ETS1 is critical for human uterine decidualization
Transcription factor ETS1 is critical for human uterine decidualization
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DOI：
10.1093/molehr/gal008
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Handwerger, S
中科院分区：
文献类型：
--
作者：
Kessler, CA;Schroeder, JK;Handwerger, S
本研究的目的是探讨转录因子 ETS1 是否在人类蜕膜化的调节中发挥关键作用。在存在或不存在阻断 ETS1 mRNA 翻译的 ETS1 反义寡核苷酸 (oligo) 的情况下，用甲羟孕酮、雌二醇 (E-2) 和二丁酰环 AMP 或前列腺素 E-2 处理，在体外使蜕膜成纤维细胞蜕膜。使用不影响 ETS1 表达和蜕膜化特定标记基因诱导的对照寡核苷酸进行对照实验。 ETS1反义寡核苷酸显着抑制ETS1蛋白表达并显着抑制ETS1作用的下游靶标。培养第 6 天，暴露于 ETS1 反义寡核苷酸的蜕膜化成纤维细胞所含的催乳素、胰岛素生长因子结合蛋白 1 (IGFBP-1) 和其他蜕膜化特异性标记物（层粘连蛋白、金属蛋白酶组织抑制剂 3 [TIMP3]、子宫内膜出血相关因子 [EBAF] 和核心蛋白聚糖）的 mRNA 比未暴露于 ETS1 反义寡核苷酸的对照细胞少 40-90%。 ETS1 反义寡核苷酸。 GAPDH mRNA 水平在蜕膜化过程中不会改变，不受 ETS1 反义或对照寡核苷酸的影响。通过蛋白质印迹分析确定，与对照细胞相比，在 ETS1 反义寡核苷酸存在下蜕膜化的细胞释放的催乳素、EBAF 和 IGFBP-1 蛋白也显着减少。总而言之，这些发现强烈表明 ETS1 在诱导人类蜕膜化中发挥着关键作用。
The aim of this study was to examine whether the transcription factor ETS1 plays a critical role in the regulation of human decidualization. Decidual fibroblast cells were decidualized in vitro by treatment with medroxyprogesterone, estradiol (E-2) and dibutyryl cyclic AMP or prostaglandin E-2 in the absence or presence of an ETS1 antisense oligonucleotide (oligo) that blocks the translation of ETS1 mRNA. Control experiments were performed using a control oligo that did not affect ETS1 expression and the induction of specific marker genes for decidualization. The ETS1 antisense oligo markedly inhibited ETS1 protein expression and significantly inhibited downstream targets of ETS1 action. On day 6 of culture, the decidualized fibroblast cells that had been exposed to the ETS1 antisense oligo contained 40-90% less mRNAs for prolactin, insulin growth factor binding protein 1 (IGFBP-1) and other decidualization-specific markers (laminin, tissue inhibitor of metalloproteinase-3 [TIMP3], endometrial bleeding associated factor [EBAF] and decorin) than those of control cells that had not been exposed to the ETS1 antisense oligo. GAPDH mRNA levels, which do not change during decidualization, were unaffected by either the ETS1 antisense or the control oligo. The cells decidualized in the presence of the ETS1 antisense oligo also released significantly less prolactin, EBAF and IGFBP-1 protein, determined by western blot analyses, than the control cells. Taken together, these findings strongly suggest that ETS1 plays a critical role in the induction of human decidualization.