摘要
胎盘发育异常与胎儿生长受限(fetal growth restriction,FGR)密切相关,但其发生机制并未被完全阐明。该文利用GEO数据库获得97个正常胎盘样本和81个FGR胎盘样本的基因芯片数据集,生物信息学分析发现,差异表达基因(DE-mRNAs)主要富集于趋化因子、HIF1α和mTOR等信号通路,参与细胞炎症、增殖、凋亡和缺氧应答反应等生物过程。PPI网络分析共发现12个关键基因(hub gene)。利用RT-qPCR验证PPI网络分析发现的关键基因(hub基因) PPBP、DUSP1、LEP和CXCL10等与生物信息学分析结果一致。FGR胎盘组织病理学检查显示,与正常胎盘相比,FGR胎盘末端绒毛发育不良、合胞体数量增加以及合体化过程受损。进一步的RT-qPCR方法证实,PPBP在FGR组胎盘中的表达低于正常组胎盘组织。PPBP在弗斯可林诱导BeWo细胞合体化过程中表达上调。干扰PPBP后BeWo细胞融合比率和合体化标记物β-hCG、Syn-1和GCM1的表达以及CREB磷酸化水平下调。研究初步发现,PPBP可能通过调控滋养细胞融合分化参与FGR的发生发展。
Abnormal placental development is associated with FGR (fetal growth restriction).However,the mechanistic bases of FGR have not been clarified.In this study,the mRNA datasets of 97 normal placental samples and 81 FGR placental samples were obtained from GEO database.Bioinformatics analysis of all the data showed that the DE-mRNAs (differentially expressed mRNAs) were mainly clustered in the chemokines,HIF1α and mTOR signaling pathways,and participated in biological processes such as cell inflammation,proliferation,apoptosis and hypoxia response.Further,12 hub genes were identified by PPI network.RT-qPCR was used to verify the hub genes,including PPBP,DUSP1,LEP and CXCL10,and the results were consistent with the bioinformatics analysis.Histopathological investigations revealed hypoplastic distal villous,increased syncytial knots and impaired syncytial layer in FGR placentas compared with normal placentas.Moreover,RT-qPCR confirmed that the expression of PPBP in the placenta of the FGR group was lower than that of the normal group.PPBP was up-regulated in the process of forskolin-induced fusion in BeWo cells.Knockdown of PPBP gene impaired the fusion of BeWo cells by inhibiting the expression of syncytialization markers,β-hCG,Syn-1,GCM1,and CREB phosphorylation.These results suggested that PPBP might be involved in the pathogenesis of FGR by inhibiting the fusion of trophoblasts.
作者
阮灵灵
刘太行
吴芝红
王永恒
丁裕斌
王应雄
付利娟
RUAN Lingling;LIU Taihang;WU Zhihong;WANG Yongheng;DING Yubin;WANG Yingxiong;FU Lijuan(Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases,College of Traditional Chinese Medicine,Chongqing 400016,China;Joint International Research Laboratory of Reproductive and Development,Department of Reproductive Biology,Chongqing 400016,China;Laboratory of Reproductive Biology,School of Public Health and Management,Chongqing Medical University,Chongqing 400016,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2021年第5期1029-1040,共12页
Chinese Journal of Cell Biology
基金
国家自然科学基金(批准号:81671493、81801458)资助的课题。