| 高龄孕妇高雄激素状态通过LAMA3-PI3K/Akt通路抑制滋养细胞侵袭的机制研究 |
| 投稿时间：2025-02-05 修订日期：2025-02-14 点此下载全文 |
| 引用本文：吴学磊,卢凤英,虞斌.高龄孕妇高雄激素状态通过LAMA3-PI3K/Akt通路抑制滋养细胞侵袭的机制研究[J].医学研究杂志,2025,54(7):54-59, 65 |
| DOI：
10.11969/j.issn.1673-548X.2025.07.011 |
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| 基金项目:国家自然科学基金资助项目(81773438)；常州市应用基础研究项目(CJ20230078)；常州市“龙城医星”卫生青年科技人才托举工程(lcyx2024002) |
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| 中文摘要:目的 旨在探讨高雄激素状态通过LAMA3-PI3K/Akt通路在高龄妊娠中引发子痫前期的机制,并评估对滋养细胞侵袭及迁移能力的影响。方法 通过双氢睾酮刺激滋养细胞,进一步使用RNA测序(RNA-Seq)、基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析筛选出差异表达基因LAMA3。采用实时荧光定量 PCR(RT-qPCR)、Western blot法检测LAMA3的mRNA和蛋白表达水平。质粒转染法获得LAMA3过表达的滋养细胞。采用基于基质的Transwall法评估细胞侵袭、划痕实验检测细胞迁移能力。结果 双氢睾酮(dihydrotestosterone,DHT)刺激抑制了滋养细胞的侵袭和迁移能力。通过RNA-seq筛选发现LAMA3可能是关键分子,进一步的Western blot法和RT-qPCR分析显示,高龄妊娠胎盘中LAMA3的蛋白和mRNA表达高于正常妊娠胎盘,且与子痫前期患者胎盘中的发现一致。LAMA3过表达抑制滋养细胞的侵袭和迁移能力,同时使PI3K和Akt的磷酸化水平上调。使用PI3K抑制剂后,细胞功能和磷酸化水平基本恢复正常水平。结论 高龄孕妇滋养细胞异常增高的雄激素水平诱导LAMA3表达发生特异性变化,并且LAMA3通过调控PI3K/Akt信号通路影响滋养细胞迁移侵袭能力。 |
| 中文关键词:高龄妊娠 胎盘 雄激素 层粘连蛋白 PI3K信号通路 |
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| Study on the Mechanism of Inhibiting Trophoblast Invasion via the LAMA3-PI3K/Akt Pathway in Hyperandrogenic States of Advanced Maternal Age. |
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| Abstract:Objective To explore the mechanism by which hyperandrogenic states induce preeclampsia in advanced maternal age through the LAMA3-PI3K/Akt pathway and assess its effects on the invasion and migration abilities of human trophoblast cells. MethodsHuman trophoblast cells were stimulated with dihydrotestosterone (DHT), followed by RNA sequencing (RNA-Seq) to identify differentially expressed genes, with gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis revealing LAMA3 as a key molecule. The mRNA and protein expression levels of LAMA3 were detected using real-time quantitative PCR (RT-qPCR) and Western blot. LAMA3-overexpressing human trophoblast cells were obtained by plasmid transfection. The invasion ability was assessed using the Matrigel-based Transwell assay, and the migration ability was evaluated by the scratch assay. Results DHT stimulation significantly inhibited the invasion and migration abilities of trophoblast cells. RNA-Seq analysis revealed that LAMA3might be a key molecule involved, and further Western blot and RT-qPCR analyses showed that the protein and mRNA expression of LAMA3 in the placenta of advanced maternal age pregnancies were significantly higher than in normal pregnancies and consistent with findings in the placenta of preeclampsia patients. Overexpression of LAMA3significantly suppressed trophoblast cell invasion and migration abilities, while also upregulating the phosphorylation levels of PI3K and Akt. Treatment with a PI3K inhibitor restored both cell function and phosphorylation levels to normal. Conclusion Elevated androgen levels in trophoblast cells from advanced maternal age induce specific changes in LAMA3 expression, and LAMA3 regulates trophoblast migration and invasion through the PI3K/Akt signaling pathway. |
| keywords:Advanced maternal age Placenta Androgens Laminin PI3K signaling pathway |
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