Transcriptional regulation of LGALS9 by HAND2 and FOXO1 in human endometrial stromal cells in women with regular cycles.
Transcriptional regulation of LGALS9 by HAND2 and FOXO1 in human endometrial stromal cells in women with regular cycles.
复制标题
具有规律周期的女性子宫内膜基质细胞中 HAND2 和 FOXO1 对 LGALS9 的转录调节。
DOI：
10.1093/molehr/gaab063
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发表时间：
2021
期刊：
影响因子：
4
通讯作者：
Okada H.
中科院分区：
文献类型：
--
作者：
Murata H;Tanaka S;Hisamatsu Y;Tsubokura H;Hashimoto Y;Kitada M;Okada H.
子宫自然杀伤细胞通过子宫内膜基质细胞（ESC）分泌的IL 15和半乳糖凝集素-9（LGALS 9）的表面抑制性受体来调节。然而，调节ESCs中LGALS 9 mRNA水平的机制尚不清楚。本研究旨在阐明LGALS 9在ESCs中的转录调控。在这里，LGALS 9 mRNA表达水平显着下降，在早期至中期分泌期的子宫内膜组织，并恢复在中期至晚期分泌期，在增殖期相比。与对照组相比，雌二醇+醋酸甲羟孕酮处理1 d后，ESCs LGALS 9 mRNA表达显著降低，12 d后表达显著升高。心脏和神经嵴衍生物表达2（HAND 2）上调LGALS 9上游区域的转录活性，叉头盒O 1（FOXO 1）下调LGALS 9上游区域的转录活性。在ESCs中，HAND 2表达在类固醇激素治疗的12天内显著增加，而FOXO 1表达在第1天显著增加，达到平台，并在治疗6天后再次显著增加。FOXO 1磷酸化水平（pFOXO 1）保持不变后，3天的治疗与类固醇激素的ESC，但显着增加后，12天的治疗。pFOXO 1不能与DNA结合，因此不能直接抑制LGALS 9的转录。因此，HAND 2的表达水平和FOXO 1的磷酸化状态可能决定LGALS 9 mRNA的表达。本研究为阐明胚胎干细胞中LGALS 9 mRNA的转录调控提供了新的分子机制，对治疗与蜕膜化失败相关的疾病具有重要意义。
Uterine natural killer cells are regulated via surface inhibitory receptors for IL15 and galectin-9 (LGALS9) secreted by endometrial stromal cells (ESCs). However, the mechanism that regulatesLGALS9mRNA levels in ESCs is unclear. The aim of this study is to clarify the transcriptional regulation ofLGALS9in ESCs. Here,LGALS9mRNA expression levels significantly decreased in the endometrial tissue in the early- to mid-secretory phase, and recovered in the mid- to late-secretory phase, compared to that in the proliferative phase. In ESCs,LGALS9mRNA expression significantly decreased following estradiol + medroxyprogesterone acetate treatment for 1 day and increased after 12 days compared to that in the control. The transcriptional activity of theLGALS9upstream region was upregulated by heart and neural crest derivatives expressed 2 (HAND2) and downregulated by forkhead box O1 (FOXO1). In ESCs,HAND2expression significantly increased throughout the 12 days treatment with steroid hormones, whereasFOXO1expression significantly increased on Day 1, reached a plateau, and significantly increased again after 6 days of treatment. Levels of FOXO1 phosphorylation (pFOXO1) remained unchanged after a 3-day treatment of ESCs with steroid hormones, but significantly increased following a 12-day treatment. pFOXO1 could not bind to the DNA and was thus unable to directly suppressLGALS9transcription. Therefore, expression level of HAND2 and phosphorylation status of FOXO1 may determineLGALS9mRNA expression. This study provides a novel molecular mechanism underlying the transcriptional regulation ofLGALS9mRNA in ESCs, which could be valuable in the treatment of diseases associated with decidualization failure.