Hu Yongfeng, Li Shaoqiang, Hong Yunhui, Peng Dongxian
Obstetrics and Gynecology Center, Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510280, China.
Department of Obstetrics, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, 528308, China.
BMC Pregnancy Childbirth. 2025 Jan 30;25(1):94. doi: 10.1186/s12884-025-07221-y.
Preeclampsia, characterized by hypertension and proteinuria during pregnancy, poses significant risks to both mother and fetus. The complement system's aberrant activation, notably the C3AR1, is important to the pathogenesis of preeclampsia, although the precise mechanisms are not fully understood.
Utilizing the Comparative Toxicogenomics Database (CTD) and Molecular Signatures Database (MSigDB), we identified complement system targets associated with preeclampsia and environmental pollutants. Expression validation was conducted through the Gene Expression Omnibus (GEO) database. Molecular docking predicted interactions between BPA, PFOS, and C3AR1. Immunohistochemical staining of 80 placental tissues (40 early-onset preeclampsia and 40 healthy controls) confirmed C3AR1 expression and its clinical correlation. Integrated bioinformatics analyses revealed C3AR1's role in preeclampsia's molecular mechanisms. Functional verification was assessed by knocking down C3AR1 in HTR-8/Svneo cells, including cell proliferation, invasion, and apoptosis.
Network pharmacology established connections between pollutants and preeclampsia, with C3AR1 as a key target. Molecular docking confirmed BPA and PFOS binding to C3AR1. Reduced C3AR1 in preeclamptic placentas correlated with maternal blood pressure, and showed high diagnostic potential (AUC = 0.95). C3AR1's involvement in preeclampsia was linked to Jak-STAT, TGF-β, and HIF-1 pathways, and associated with NK cell and M1 macrophage activity. C3AR1 knockdown in HTR-8/Svneo cells decreased proliferation and invasion, and increased apoptosis.
C3AR1 expression is diminished in preeclampsia placental tissues, correlating with disease severity, suggesting its potential as a biomarker. It is crucial for cellular functions and inflammation, with future studies aiming to leverage this for novel preeclampsia treatments.
Not applicable.
子痫前期的特征是孕期高血压和蛋白尿，对母亲和胎儿均构成重大风险。补体系统的异常激活，尤其是C3AR1，对子痫前期的发病机制很重要，尽管其确切机制尚未完全明确。
利用比较毒理基因组学数据库（CTD）和分子特征数据库（MSigDB），我们确定了与子痫前期和环境污染物相关的补体系统靶点。通过基因表达综合数据库（GEO）进行表达验证。分子对接预测了双酚A（BPA）、全氟辛烷磺酸（PFOS）与C3AR1之间的相互作用。对80份胎盘组织（40例早发型子痫前期和40例健康对照）进行免疫组织化学染色，证实了C3AR1的表达及其临床相关性。综合生物信息学分析揭示了C3AR1在子痫前期分子机制中的作用。通过在HTR-8/Svneo细胞中敲低C3AR1评估功能验证，包括细胞增殖、侵袭和凋亡。
网络药理学建立了污染物与子痫前期之间的联系，C3AR1是关键靶点。分子对接证实BPA和PFOS与C3AR1结合。子痫前期胎盘中C3AR1的减少与孕妇血压相关，并显示出较高的诊断潜力（曲线下面积[AUC]=0.95）。C3AR1参与子痫前期与Jak-STAT、TGF-β和HIF-1通路有关，并与自然杀伤（NK）细胞和M1巨噬细胞活性相关。在HTR-8/Svneo细胞中敲低C3AR1可降低细胞增殖和侵袭，并增加细胞凋亡。
子痫前期胎盘组织中C3AR1表达降低，与疾病严重程度相关，提示其作为生物标志物的潜力。它对细胞功能和炎症至关重要，未来的研究旨在利用这一点开发新的子痫前期治疗方法。
不适用。
