Deletion of Insulin-like growth factor II mRNA-binding protein 3 participates in the pathogenesis of recurrent spontaneous abortion by inhibiting IL-10 secretion and inducing M1 polarization.
Deletion of Insulin-like growth factor II mRNA-binding protein 3 participates in the pathogenesis of recurrent spontaneous abortion by inhibiting IL-10 secretion and inducing M1 polarization.
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DOI：
10.1016/j.intimp.2022.109473
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发表时间：
2022-12
影响因子：
5.6
通讯作者：
Yu-wei Zhang;Fangfang Dai;Dongyong Yang;Ya-jing Zheng;Rong-hui Zhu;Mali Wu;Zhi-Min Deng;Zitao W
中科院分区：
文献类型：
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作者：
Yu-wei Zhang;Fangfang Dai;Dongyong Yang;Ya-jing Zheng;Rong-hui Zhu;Mali Wu;Zhi-Min Deng;Zitao W
胰岛素样生长因子II mRNA结合蛋白3（IGF2BP3）已被证明影响滋养层功能和胚胎发育，但其在复发性自然流产（RSA）中的作用和潜在机制尚不清楚。 RSA是一种复杂的生殖疾病，给患者造成身心损害。近年来，许多研究发现，免疫微环境对于维持母胎界面成功妊娠至关重要。因此，本研究旨在探讨IGF2BP3在影响巨噬细胞极化中的作用及其可能机制。在本文中，我们发现人类和RSA小鼠模型的胎盘绒毛样本中IGF2BP3表达降低，并且HTR8/SVneo细胞中IGF2BP3的敲低促进M1 Mφ极化。结合RNA测序分析，我们发现IGF2BP3可能通过影响滋养层细胞因子的表达，特别是IL-10的分泌来调节Mφ极化。进一步的机制研究表明，IGF2BP3 的敲低通过激活 NF-κB 途径降低了 IL-10 的表达。此外，我们发现M2 Mφ促进滋养层侵袭，而不是IGF2BP3依赖性的。我们的研究揭示了RSA患者母胎界面滋养层细胞与巨噬细胞之间的相互作用，为其诊断和治疗RSA患者提供理论指导。
Insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3) has been proved to affect trophoblast function and embryonic development, but its role and potential mechanism in recurrent spontaneous abortion (RSA) are not clear. RSA is a complex reproductive disease, causing physical and mental damage to patients. In recent years, many studies have found that immune microenvironment is vital to maintain successful pregnancy in the maternal fetal interface. Therefore, this study aims to explore the role of IGF2BP3 in affecting macrophage polarization and its possible mechanism. In this article, we found that IGF2BP3 expression was decreased in placental villous samples of human and RSA mouse model, and knockdown of IGF2BP3 in HTR8/SVneo cells promotes M1 Mφ polarization. Combining with RNA sequencing analysis, we found that IGF2BP3 may regulate the Mφ polarization by affecting the expression of trophoblast cytokines, especially IL-10 secretion. Further mechanistic studies showed that knockdown of IGF2BP3 decreased expression of IL-10 by activating NF-κB pathway. Moreover, we found that M2 Mφ promote trophoblast invasion not IGF2BP3 dependent. Our study reveals the interaction between trophoblast cells and macrophages at the maternal-fetal interface of RSA patients, and will provide theoretical guidance for its diagnosis and treatment of RSA patients.