Palma-Vera Sergio E, Einspanier Ralf
Institute of Veterinary Biochemistry, Freie Universität Berlin, Oertzenweg 19b, 14163, Berlin, Germany.
Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
Reprod Biol Endocrinol. 2016 Apr 18;14:22. doi: 10.1186/s12958-016-0156-y.
In ruminants, embryo implantation depends on progesterone (P4) and interferon tau (IFNT) controlling endometrial function. IFNT antagonizes bovine endometrial cells (BEND) response to phorbol 12,13-dibutyrate (PDBU) through posttranscriptional regulation of gene expression. We have previously described microRNAs (miRNAs) profiles in bovine endometrium, detecting miR-106a, relevant for embryo maternal communication. In this study, we investigated the expression miR-106a and genes for prostaglandin-endoperoxide synthase 2 (PTGS2), phospholipase A2, group IVA (PLA2G4A), estrogen receptor 1 (ESR1) and progesterone receptor (PR) in response to IFNT in BEND cells and searched for interferon responsive factors (IRFs) binding sites in their promoter genomic regions. The aim of this study was to unravel the molecular mechanisms involved in IFNT signalling and its regulation of miR-106a.
PTGS2 showed increased expression under PDBU, which was antagonized by IFNT. IFNT induced expression of PR and miR-106a and downregulation of ESR1 and PR. Bioinformatic analyses detected that PLA2G4A was associated to IRF-1 and IRF-6, while ESR1, PR and PTGS2 were associated to only IRF-6. All genes exhibit one motif per IRF, except miR-106a that had three binding sites for IRF-6.
We report the IFNT regulatory effect on miR-106a expression through IRF-6 in bovine endometrial cells. We identified a set of potential binding sites for IRF-1 and IRF-6 within the bovine genome. A set of candidate gene regions could be characterized where IFNT can act via IRFs to regulate the expression of proteins and miRNAs. Future studies will use these data to detect new IFNT regulatory mechanisms in the endometrium.
在反刍动物中，胚胎着床依赖于孕酮（P4）和干扰素τ（IFNT）对子宫内膜功能的调控。IFNT通过基因表达的转录后调控拮抗牛子宫内膜细胞（BEND）对佛波酯12,13 - 二丁酸酯（PDBU）的反应。我们之前已描述了牛子宫内膜中的微小RNA（miRNA）谱，检测到与胚胎 - 母体通讯相关的miR - 106a。在本研究中，我们调查了BEND细胞中miR - 106a以及前列腺素内过氧化物合酶2（PTGS2）、IVA型磷脂酶A2（PLA2G4A）、雌激素受体1（ESR1）和孕酮受体（PR）基因对IFNT的反应，并在它们的启动子基因组区域搜索干扰素反应因子（IRF）结合位点。本研究的目的是揭示IFNT信号传导及其对miR - 106a调控所涉及的分子机制。
PTGS2在PDBU作用下表达增加，而IFNT可拮抗这一作用。IFNT诱导PR和miR - 106a的表达，并下调ESR1和PR。生物信息学分析检测到PLA2G4A与IRF - 1和IRF - 6相关，而ESR1、PR和PTGS2仅与IRF - 6相关。除miR - 106a有三个IRF - 6结合位点外，所有基因每个IRF均呈现一个基序。
我们报道了IFNT通过IRF - 6对牛子宫内膜细胞中miR - 106a表达的调控作用。我们在牛基因组中鉴定出一组IRF - 1和IRF - 6的潜在结合位点。可以对一组候选基因区域进行表征，IFNT可通过IRF在此处发挥作用来调节蛋白质和miRNA的表达。未来的研究将利用这些数据来检测子宫内膜中IFNT的新调控机制。
