Identification of genes in the ovine endometrium regulated by interferon τ independent of signal transducer and activator of transcription 1
Identification of genes in the ovine endometrium regulated by interferon τ independent of signal transducer and activator of transcription 1
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DOI：
10.1210/en.2003-0665
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Spencer, TE
中科院分区：
文献类型：
--
作者：
Kim, S;Choi, Y;Spencer, TE
干扰素tau（Interferon tau，IFNtau）是由孕体滋养外胚层产生的一种I型干扰素，通过信号转导和转录激活因子1（STAT 1）依赖性途径，增加绵羊子宫内膜间质和腺上皮（GE）中许多I型干扰素刺激基因（ISG）的表达。在STAT 1阴性的子宫内膜腔上皮（LE）中，大多数ISG不被IFNtau诱导或增加。目的是使用DNA微阵列和人细胞系以STAT 1非依赖性方式鉴定由IFNtau调控的基因。使用Affytron人基因组U95 Av 2微阵列分析来自人2fTGH和U3 A（STAT 1无效2fTGH）细胞系的RNA，所述细胞系用无IFN tau或重组羊IFN tau刺激24小时。在2fTGH细胞中，IFNtau使101个基因的表达增加至少2倍，包括IFN诱导的56-kDa蛋白（IFI 56）、ISG 12或p27和鸟苷酸结合蛋白亚型I（GBP 2）。在U3 A细胞中，IFNtau使66个基因的表达增加至少2倍，包括Wnt 7a。稳态水平的IFI 56，ISG 12，GBP-2，Wnt 7a mRNA增加在绵羊子宫内膜之间的第10和16天的怀孕，但不是在发情周期。GBP-2和IFI 56 mRNA仅在绵羊子宫内膜基质中表达，ISG 12在LE和GE中表达，Wnt 7a仅在LE中表达。子宫内输注绵羊IFNtau增加了周期性母羊子宫内膜中所有四种基因的表达。因此，IFNtau在子宫内膜LE和U3 A细胞中不依赖于STAT 1调节基因，而在子宫内膜基质和2fTGH细胞中依赖于STAT 1。这些IFN τ刺激的基因可能在建立子宫对胚胎和孕体着床的接受性中很重要，因为它们在不同物种的子宫内膜中具有阶段特异性。
Interferon tau (IFNtau), a type I IFN produced by the conceptus trophectoderm, increases many type I IFN-stimulated genes (ISGs) in the ovine uterine endometrial stroma and glandular epithelium (GE) using signal transducer and activator of transcription 1 (STAT1)-dependent pathways. Most ISGs are not induced or increased by IFNtau in the STAT1-negative endometrial luminal epithelium ( LE). The objective was to identify genes regulated by IFNtau in a STAT1-independent manner using DNA microarray and human cell lines. The RNA from human 2fTGH and U3A ( STAT1 null 2fTGH) cell lines, stimulated for 24 h with nothing or recombinant ovine IFNtau, was profiled using an Affymetrix human genome U95Av2 microarray. In 2fTGH cells, IFNtau increased the expression of 101 genes at least 2-fold, including IFN-inducible 56-kDa protein (IFI56), ISG12 or p27, and guanylate binding protein isoform I (GBP2). In U3A cells, IFNtau increased expression of 66 genes at least 2-fold, including Wnt7a. Steady-state levels of IFI56, ISG12, GBP-2, and Wnt7a mRNAs increased in the ovine uterine endometrium between d 10 and 16 of pregnancy but not during the estrous cycle. GBP-2 and IFI56 mRNAs were expressed only in endometrial stroma, ISG12 in both LE and GE, and Wnt7a only in LE of the ovine uterus. Intrauterine infusion of ovine IFNtau increased expression of all four genes in the endometrium of cyclic ewes. Therefore, IFNtau does regulate genes independent of STAT1 in the endometrial LE and U3A cells and dependent on STAT1 in the endometrial stroma and 2fTGH cells. These IFNtau-stimulated genes may be important in establishment of uterine receptivity to the embryo and conceptus implantation given their stage-specificity in endometrium across diverse species.