HMGB1 promotes immune abnormalities in preeclampsia by recruiting monocyte/decidual macrophages and inducing M1 polarization.

IF 3.1 2区 生物学 Q2 REPRODUCTIVE BIOLOGY
Xixi Deng, Xueqi Li, Guiqiong Huang, Jiani Zhang, Tingting Xu, Ying Feng, Xiaodong Wang
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Abstract

Preeclampsia (PE) is a severe pregnancy complication associated with immune imbalance and placental hypoxia stress. Decidua macrophages (dMφ) are essential at maternal fetal interface, which is abnormally activated and excessively transformed to the M1-phenotype in PE. High mobility group box 1(HMGB1), released from necrotic cells after injury, accumulates in the placenta and peripheral blood of patients with PE. Therefore, this study aims to investigate the interaction between macrophages and trophoblasts, exploring how HMGB1 affects macrophage functions and its potential involvement in the pathophysiology of PE. Decidua tissue was obtained from 11 women with severe pre-eclampsia (sPE), 13 women with pre-eclampsia (PE), and 13 women with normal pregnancies. HMGB1 levels in decidua were evaluated by immunohistochemistry (IHC), western blot, and qPCR. Additionally, primary dMφ and peripheral blood monocytes (pMo) were isolated to develop a co-culture model simulating maternal fetal interface cell model of PE. Flow cytometric analysis and in vitro cell migration assay investigated the interaction between macrophages and HMGB1. This study identified elevated HMGB expression in PE patients. HMGB1 expressed widely in trophoblast, decidual stromal cells, and the extracellular matrix. Furthermore, hypoxia induced trophoblast to express and secrete HMGB1, promoting pMo and dMφ migration. Additionally, HMGB1 recruited monocyte-induced macrophages (pMφ) and modulated M1 macrophage polarization. HMGB1 is increased at the maternal-fetal interface of PE, which recruits monocytes and macrophages and induces their polarization to M1. This study offers insights into the suppressive effects of the crosstalk between dMφ and trophoblasts at the maternal-fetal interface, lending credence to macrophage-targeted interventions of PE as a potential therapeutic strategy.

HMGB1通过募集单核/蜕膜巨噬细胞和诱导M1极化促进子痫前期免疫异常。
子痫前期(PE)是一种严重的妊娠并发症,与免疫失衡和胎盘缺氧应激有关。蜕膜巨噬细胞(dMφ)在母胎界面是必不可少的,在PE中被异常激活并过度转化为m1表型。高迁移率组框1(HMGB1),从坏死细胞损伤后释放,在PE患者胎盘和外周血中积累。因此,本研究旨在研究巨噬细胞与滋养细胞之间的相互作用,探讨HMGB1如何影响巨噬细胞功能及其在PE病理生理中的潜在作用。从11例重度子痫前期妇女(sPE)、13例子痫前期妇女(PE)和13例正常妊娠妇女中获得蜕膜组织。采用免疫组化(IHC)、western blot和qPCR检测蜕膜中HMGB1水平。此外,分离原代dMφ和外周血单核细胞(pMo),建立模拟PE母胎界面细胞模型的共培养模型。流式细胞分析和体外细胞迁移实验研究了巨噬细胞与HMGB1的相互作用。本研究发现在PE患者中HMGB表达升高。HMGB1在滋养细胞、蜕质细胞和细胞外基质中广泛表达。缺氧诱导滋养细胞表达和分泌HMGB1,促进pMo和dMφ迁移。HMGB1募集单核细胞诱导的巨噬细胞(pMφ),调节M1巨噬细胞极化。HMGB1在PE母胎交界面增加,募集单核细胞和巨噬细胞,诱导其向M1极化。这项研究提供了dMφ和母胎界面滋养细胞之间串扰的抑制作用,为巨噬细胞靶向PE干预作为一种潜在的治疗策略提供了证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology of Reproduction
Biology of Reproduction 生物-生殖生物学
CiteScore
6.30
自引率
5.60%
发文量
214
审稿时长
1 months
期刊介绍: Biology of Reproduction (BOR) is the official journal of the Society for the Study of Reproduction and publishes original research on a broad range of topics in the field of reproductive biology, as well as reviews on topics of current importance or controversy. BOR is consistently one of the most highly cited journals publishing original research in the field of reproductive biology.
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