The roles of NLRP3 and prostaglandin E2 in mediating bidirectional cross-talk between bovine endometrial fibroblasts and M2 macrophages

IF 3.3 2区农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Animal Reproduction Science Pub Date : 2025-08-20 DOI:10.1016/j.anireprosci.2025.107972

Jiamin Zhao , Haixia Bao , Wenhui Bao , Zhiguo Gong , Yunhe Fu , Xiaoyu Hu , Yanqin Dong , Wei Mao , Shuang Feng , Shuangyi Zhang

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引用次数: 0

Abstract

The bovine endometrium undergoes dynamic structural and functional changes during the estrous cycle, driven by intricate cellular interactions and a complex network of chemokines, cytokines, and growth factors. Among the key cell types, endometrial stromal fibroblasts and M2 macrophages are essential for anti-inflammatory responses and tissue remodeling. However, their bidirectional cross-talk remains poorly characterized. In this study, we investigated fibroblast-macrophage interactions using a conditioned medium-based co-culture system. M2 macrophages were treated with myofibroblast-conditioned medium (MFbCM), while myofibroblasts were treated with M2 macrophage-conditioned medium (M2ø CM), allowing detailed analysis of reciprocal regulatory effects. M2ø CM significantly upregulated fibroblast expression of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9), suggesting M2 macrophage-mediated modulation of fibroblast remodeling activity. Conversely, MFbCM enhanced interleukin-10 (IL-10) and arginase expression in M2 macrophages, supporting fibroblast-driven polarization. Notably, both conditioned media increased expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) in target cells. Inhibition of NLRP3 using the selective inhibitor MCC950 revealed that the NLRP3-prostaglandin E₂ (PGE₂) axis plays a pivotal role in mediating the cross-talk between these cell types. Collectively, our findings reveal a pivotal NLRP3-PGE₂ signaling axis in the regulation of fibroblast-macrophage interactions, offering novel insights into the mechanisms underlying bovine endometrial homeostasis and remodeling.

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NLRP3和前列腺素E2在介导牛子宫内膜成纤维细胞与M2巨噬细胞双向交流中的作用

在发情周期中，牛子宫内膜在复杂的细胞相互作用和复杂的趋化因子、细胞因子和生长因子网络的驱动下，经历了动态的结构和功能变化。在关键细胞类型中，子宫内膜间质成纤维细胞和M2巨噬细胞对抗炎反应和组织重塑至关重要。然而，它们的双向串扰特性仍然很差。在这项研究中，我们使用条件培养基共培养系统研究了成纤维细胞与巨噬细胞的相互作用。M2巨噬细胞用肌成纤维细胞条件培养基（MFbCM）处理，而肌成纤维细胞用M2巨噬细胞条件培养基（M2ø CM）处理，可以详细分析相互调节作用。M2ø CM显著上调成纤维细胞生长因子-2 （FGF-2）、血管内皮生长因子（VEGF）和基质金属蛋白酶-9 （MMP-9）的表达，提示M2巨噬细胞介导了成纤维细胞重塑活性的调节。相反，MFbCM增强了M2巨噬细胞中白细胞介素-10 （IL-10）和精氨酸酶的表达，支持成纤维细胞驱动的极化。值得注意的是，两种条件培养基均增加了靶细胞中nod样受体家族pyrin domain containing 3 （NLRP3）的表达。使用选择性抑制剂MCC950抑制NLRP3表明NLRP3-前列腺素E2 （PGE2）轴在介导这些细胞类型之间的串扰中起关键作用。总之，我们的研究结果揭示了一个关键的NLRP3-PGE2信号轴在成纤维细胞-巨噬细胞相互作用的调节中，为牛子宫内膜稳态和重塑的机制提供了新的见解。

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来源期刊

Animal Reproduction Science 农林科学-奶制品与动物科学

CiteScore

4.50

自引率

9.10%

发文量

136

审稿时长

54 days

期刊介绍： Animal Reproduction Science publishes results from studies relating to reproduction and fertility in animals. This includes both fundamental research and applied studies, including management practices that increase our understanding of the biology and manipulation of reproduction. Manuscripts should go into depth in the mechanisms involved in the research reported, rather than a give a mere description of findings. The focus is on animals that are useful to humans including food- and fibre-producing; companion/recreational; captive; and endangered species including zoo animals, but excluding laboratory animals unless the results of the study provide new information that impacts the basic understanding of the biology or manipulation of reproduction. The journal''s scope includes the study of reproductive physiology and endocrinology, reproductive cycles, natural and artificial control of reproduction, preservation and use of gametes and embryos, pregnancy and parturition, infertility and sterility, diagnostic and therapeutic techniques. The Editorial Board of Animal Reproduction Science has decided not to publish papers in which there is an exclusive examination of the in vitro development of oocytes and embryos; however, there will be consideration of papers that include in vitro studies where the source of the oocytes and/or development of the embryos beyond the blastocyst stage is part of the experimental design.