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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引用次数: 0

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.

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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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