Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.
Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.
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DOI：
10.1371/journal.pone.0171858
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Imakawa K
中科院分区：
文献类型：
--
作者：
Kusama K;Bai R;Nakamura K;Okada S;Yasuda J;Imakawa K
在反刍动物中，干扰素tau（IFNT）是由孕体的单核滋养外胚层产生的妊娠识别蛋白，并且在围附着期期间分泌到子宫腔中。在我们之前的研究中，在围附着期从牛孕体获得的高通量RNA测序（RNA-seq）数据鉴定了两种IFNT mRNA，IFNT 2和IFNTc 1。然而，这些IFNT变体各自如何调节子宫内膜基因表达尚未得到表征。使用RNA-seq分析，我们评估了IFNT 2和IFNTc 1如何影响原代牛子宫内膜上皮细胞（EECs）的转录表达。IFNT处理诱导了348个差异表达基因（DEG）;然而，IFNT 2或IFNTc 1处理的EC中几乎没有DEG，表明IFNT 2诱导的DEG与IFNTc 1处理诱导的DEG相似。在计算机模拟分析中，我们确定了四种IFNT 2和IFNTc 1诱导的途径：1）II型干扰素信号传导，2）蛋白酶体降解，3）III型干扰素信号传导和4）DNA损伤反应。我们进一步证明了IFNT 2和IFNTc 1上调了几种转录因子，其中叉头框S1（FOXS 1）被鉴定为最高表达的基因。此外，在IFNT 2或IFNTc 1处理的EECs中，FOXS 1的敲低类似地下调了包括IRF 3和IRF 9在内的9个基因，并上调了包括STAT 1、STAT 2和IRF 8在内的9个基因。这些代表了第一次证明，每个IFNT对EECs的影响进行了研究，并表明子宫内膜的反应以及信号传导机制是相似的两个IFNT变体存在于子宫内。
In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero.