趋化素通过戊糖磷酸途径促进胎盘滋养细胞侵袭和螺旋动脉重构

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-23 DOI:10.1016/j.lfs.2025.123645

Jiaxuan Cai , Xinyue Han , Suohao Peng , Jie Chen , Jian V. Zhang , Chen Huang

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引用次数: 0

摘要

目的滋养细胞的侵袭和螺旋动脉的重塑是胎盘成功的必要过程。滋养细胞侵袭缺陷与妊娠并发症密切相关，包括流产和先兆子痫。在本研究中，我们研究趋化素在滋养细胞侵袭和动脉重塑中的作用，并探讨其潜在机制。主要方法采用免疫组化染色法检测小鼠胎盘和人胎盘早期不同时期趋化素的表达。采用外源性趋化素肽（Chemerin） KO和lps处理小鼠，评估滋养细胞巨细胞（TGC）侵袭、动脉重塑和NK细胞浸润。在E8.5上进行Chemerin KO和lps处理的蜕膜代谢产物档案，并测量相关酶的表达。通过人滋养层HTR-8细胞迁移和戊糖磷酸途径酶的表达进一步检测Chemerin的功能。关键发现schemerin在小鼠侵袭性TGC和人绒毛外滋养细胞中高表达。妊娠小鼠缺乏趋化素和LPS处理后，胎盘TGC侵袭、螺旋动脉重塑、蜕膜NK细胞浸润受损，其主要原因是戊糖磷酸通路（PPP）代谢物及G6PD、RPIA表达下调。趋化素激活PPP加速HTR-8细胞迁移。外源性趋化素显著减轻lps处理小鼠TGC侵袭缺陷和动脉重构，促进NK浸润和母体血液灌注。意义本研究描述了趋化素在滋养细胞侵袭和动脉重塑中不可或缺的作用，并提示其在妊娠并发症流产和先兆子痫中的潜在应用。

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Chemerin facilitates placental trophoblast invasion and spiral artery remodeling through the pentose phosphate pathway

Aims

The invasion of trophoblasts and remodeling of spiral arteries are the requisite processes for successful placentation. A defect of trophoblast invasion is closely associated with pregnancy complications, including miscarriage and preeclampsia. In this study, we investigated the function of chemerin in trophoblast invasion and artery remodeling and explored the underlying mechanism in this process.

Main methods

Immunostaining was performed to examine chemerin expression in different days of mouse placenta and early stage of human placenta. Chemerin KO and LPS-treated mice, with exogenous chemerin peptide, were used to evaluate trophoblast giant cells (TGC) invasion, artery remodeling, and NK cell infiltration. Chemerin KO and LPS-treated decidua on E8.5 were conducted in metabolites file and measured related enzymes' expression. Chemerin’s function was further examined by human trophoblast HTR-8 cell migration and the enzymes expression in the pentose phosphate pathway.

Key findings

Chemerin has high expression in mouse-invasive TGC and human extra-villous trophoblast cells. Deficiency of chemerin and LPS treatment in pregnant mice impaired placental TGC invasion, spiral artery remodeling, and NK cell infiltration in decidua, which mainly attributed to the downregulation of metabolites and G6PD and RPIA expression in pentose phosphate pathway (PPP). Chemerin activated the PPP to accelerate HTR-8 cell migration. Exogenous chemerin administration remarkably attenuated the defect of TGC invading and artery remodeling in LPS-treated mice, and promoted NK infiltration and maternal blood perfusion.

Significance

This study described the indispensable role of chemerin in trophoblast invasion and arterial remodeling, and suggested its potential application in pregnancy complications miscarriage and preeclampsia.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

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