PPBP Participates in Fetal Growth Restriction through Regulating Trophoblast Fusion
RUAN Lingling1,2, LIU Taihang3, WU Zhihong3, WANG Yongheng3, DING Yubin2,3, WANG Yingxiong2, FU Lijuan1*
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.
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