Pentraxin 3 (PTX3), a multimeric glycoprotein, is implicated in various biological functions. PTX3 was shown to be elevated in the corpus luteum (CL) of early pregnant ewes; however, its role in sheep or other ruminants' CL during this reproductive stage or how it is regulated remain unknown. Here we explored the role of PTX3 and its relationship with interferon-tau (IFNT; the pregnancy recognition signaling molecule during early pregnancy in domestic ruminants) in bovine luteinized granulosa cells (LGCs). IFNT robustly elevated PTX3 expression in bovine LGCs, and significantly stimulated its expression in luteal endothelial cells, along with CL slices; yet, LGCs were the most responsive and sensitive among these luteal models. ALK2/ALK3/ALK6 kinase inhibitor, dorsomorphin, dose-dependently inhibited basal and IFNT-elevated PTX3 expression in LGCs. In contrast, ALK4/5/7 inhibitor, SB431542, did not alter basal and TGFB1-induced PTX3. We found that recombinant human PTX3 itself moderately but significantly increases LGC numbers. Because PTX3 is highly expressed in bovine LGCs, we next examined the impact of lowering endogenous PTX3 levels with siRNA. PTX3 silencing decreased the viable cell numbers and reversed IFNT actions on cell viability, percentage of proliferating cells, and on two key survival/death genes: BIRC5 encoding surviving protein, and FASL - a death-inducing signal. Interestingly, thrombospondin-1, a known luteal proapoptotic factor, was inversely related to PTX3 in LGCs. Together, these findings suggest a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage.

中文翻译：

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Pentraxin-3 在牛黄体化颗粒细胞中介导干扰素 Tau 的促存活作用

Pentraxin 3 (PTX3) 是一种多聚体糖蛋白，与多种生物学功能有关。PTX3 显示在早期怀孕母羊的黄体 (CL) 中升高；然而，它在这个繁殖阶段在绵羊或其他反刍动物的 CL 中的作用或如何调节仍然未知。在这里，我们探讨了 PTX3 的作用及其与牛黄素化颗粒细胞 (LGC) 中干扰素-tau（IFNT；家养反刍动物早期妊娠期间的妊娠识别信号分子）的关系。IVT 可显着提高牛 LGC 中 PTX3 的表达，并显着刺激其在黄体内皮细胞和 CL 切片中的表达；然而，LGCs 是这些黄体模型中反应最快和最敏感的。ALK2/ALK3/ALK6 激酶抑制剂，dorsomorphin，剂量依赖性抑制 LGC 中基础和 IFNT 升高的 PTX3 表达。相比之下，ALK4/5/7 抑制剂 SB431542 没有改变基础和 TGFB1 诱导的 PTX3。我们发现重组人 PTX3 本身适度但显着增加 LGC 数量。因为 PTX3 在牛 LGC 中高度表达，我们接下来检查了用 siRNA 降低内源性 PTX3 水平的影响。PTX3 沉默减少了活细胞数量并逆转了 IFNT 对细胞活力、增殖细胞百分比和两个关键存活/死亡基因的作用：BIRC5 编码存活蛋白和 FASL - 一种死亡诱导信号。有趣的是，血小板反应蛋白-1（一种已知的黄体促凋亡因子）与 LGC 中的 PTX3 呈负相关。总之，这些发现表明 PTX3 在怀孕早期具有新的作用，