中国妇幼健康研究2025，Vol.36Issue(7)：7-18,12.DOI:10.3969/j.issn.1673-5293.2025.07.002
生长分化因子-8通过调控性别决定区Y框蛋白2表达影响滋养层细胞增殖、迁移和侵袭的研究
GDF-8 regulates trophoblast cell proliferation,migration,and invasion by modulating SOX2 expression
摘要
Abstract
Objective To investigate the expression of growth differentiation factor-8(GDF-8)in the placental tissue of patients with preeclampsia(PE)and to explore the molecular mechanism by which GDF-8 regulates the proliferation,migration,and invasion of trophoblast cells by modulating the expression of sex determining region Y-box 2(SOX2).Methods Placental tissues were collected from PE patients and healthy pregnant women undergoing cesarean section.The mRNA expression level of GDF-8 in placental tissues was detected by quantitative real-time PCR(qRT-PCR).The human chorionic trophoblast cell line HTR-8/SVneo was cultured in vitro.Cells were transfected with pcDNA-GDF-8,pcDNA-NC1,pcDNA-SOX2,pcDNA-NC2,pcDNA-GDF-8+si-SOX2,and pcDNA-GDF-8+si-NC,respectively.Cells cultured under normal conditions without transfection were used as the control.The mRNA expression levels of GDF-8 and SOX2 were detected by qRT-PCR.Cell proliferation was assessed using the CCK-8 assay.The proportion of EdU-positive proliferating cells was calculated.Cell migration ability was evaluated using a scratch assay,and invasion ability was assessed using the Transwell chamber assay.Western blot analysis was used to determine the protein expression levels of GDF-8,SOX2,proliferating cell nuclear antigen(PCNA),Ki67,matrix metalloproteinase-2(MMP-2),and MMP-9.Results Compared with normal pregnant women,the expression level of GDF-8 mRNA in the placental tissue of PE patients was significantly decreased(t=35.174,P＜0.001).Compared with the pcDNA-NC1 group,the HTR-8/SVneo cells in the pcDNA-GDF-8 group showed significantly enhanced proliferation,increased proportion of EdU-positive cells,improved scratch wound healing rate,upregulated expression of PCNA,Ki67,MMP-2,and MMP-9 proteins,and increased number of invading cells(t=21.052,35.174,47.602,19.751,20.519,28.412,25.016 and 69.453,respectively,P＜0.001).Both SOX2 mRNA and protein expression levels were also significantly elevated in these cells(t=31.520 and 26.478,respectively,P＜0.001).Compared with the pcDNA-NC2 group,the pcDNA-SOX2 group exhibited enhanced cell proliferation,higher proportion of EdU-positive cells,improved scratch wound healing rate,upregulated expression of PCNA,Ki67,MMP-2,and MMP-9 proteins,and increased cell invasion(t=18.025,26.510,32.518,22.690,21.547,24.751,20.957 and 59.120,respectively,P＜0.001).In contrast,compared with the pcDNA-GDF-8+si-NC group,cells in the pcDNA-GDF-8+si-SOX2 group showed reduced proliferation,lower proportion of EdU-positive cells,decreased scratch healing rate,downregulated expression of PCNA,Ki67,MMP-2,and MMP-9,and reduced cell invasion(t=13.085,19.250,26.510,15.420,14.862,24.599,26.743 and 72.061,respectively,P＜0.001).Conclusion The expression of GDF-8 is decreased in the placental tissue of patients with PE.Overexpression of GDF-8 may promote the proliferation,migration,and invasion of trophoblast cells by inducing SOX2 expression,thereby influencing the occurrence and development of PE.关键词
子痫前期/滋养层细胞/生长分化因子-8/性别决定区Y框蛋白2/增殖/迁移/侵袭Key words
preeclampsia/trophoblast cell/GDF-8/SOX2/proliferation/migration/invasion分类
医药卫生引用本文复制引用
梁芳,吴珊珊,刘广申,钟雪辉,王建华..生长分化因子-8通过调控性别决定区Y框蛋白2表达影响滋养层细胞增殖、迁移和侵袭的研究[J].中国妇幼健康研究,2025,36(7):7-18,12.基金项目
湖南省卫生健康委科研计划项目(B202305016863) （B202305016863）
