首页|子痫前期miR-4531/CX3CL1信号轴参与血管损伤的体外研究

子痫前期miR-4531/CX3CL1信号轴参与血管损伤的体外研究

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目的 探讨miR-4531/CX3CL1 信号通路在子痫前期血管损伤中的作用,寻找早期诊断和防治子痫前期的潜在靶点.方法 选择 2021 年 10 月至 2022 年 12 月在复旦大学附属闵行医院诊断为晚发型子痫前期的 10 例患者及同期10 例正常妊娠者的胎盘组织样本,用qRT-PCR检测miR-4531 和CX3CL1 在胎盘组织中的表达水平.通过lipofectamine 2000 进行体外细胞转染,用荧光素酶报告基因实验确定miR-4531 与CX3CL1 之间的结合关系.检测中性粒细胞的凋亡,人脐静脉内皮细胞(HUVECs)的迁移、修复、集落形成、游离DNA(cfDNA)释放等.结果 子痫前期患者胎盘组织中miR-4531 下调、CX3CL1 上调(P<0.05).荧光素酶报告基因实验显示,miR-4531 与CX3CL1 之间存在直接结合关系.上调miR-4531 促进HUVECs的迁移、增殖和修复,抑制缺氧条件下HUVECs中cfDNA的释放及中性粒细胞的凋亡(P<0.05);下调miR-4531 抑制HUVECs的增殖、迁移和修复,增强缺氧条件下HUVECs中cfDNA的释放,促进中性粒细胞的凋亡(P<0.05).结论 子痫前期患者胎盘组织中miR-4531 表达下调,可能通过靶向调控CX3CL1 通路导致缺氧条件下血管内皮损伤和异常高凝血状态,是PE潜在的治疗靶点.
Effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia in vitro
Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia,and to search possible targets for early diagnosis and prevention of preeclampsia.Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital,Fudan University from October 2021 to December 2022.The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR.Cell transfection was performed by lipofectamine 2000 in vitro.The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay.The apoptosis of neutrophils,the migration,repair,colony formation and cell-free DNA(cfDNA)release of human umbilical vein endothelial cells(HUVECs)were detected.Results MiR-4531 was significantly downregulated,and CX3CL1 was upregulated in placental tissues of preeclampsia patients(P<0.05).Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1.Upregulation of miR-4531significantly promoted the migration,proliferation,repair,and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition(P<0.05).However,downregulation of miR-4531 obviously inhibited the proliferation,migration,repair,and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition(P<0.05).Conclusions The miR-4531 is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia.It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

preeclampsiamiR-4531CX3CL1human umbilical vein endothelial cellcell-free DNA

王曼、李骏、李航、宋青、刘艳、王海丽、王晓、程群仙、胡峥、徐灵

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复旦大学附属闵行医院妇产科,上海 201199

子痫前期 miR-4531 CX3CL1 人脐静脉内皮细胞 细胞游离DNA

2024

中国临床医学
复旦大学附属中山医院

中国临床医学

CSTPCD
影响因子:1.002
ISSN:1008-6358
年,卷(期):2024.31(6)