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THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia
Genes & Diseases ( IF 6.9 ) Pub Date : 2020-06-08 , DOI: 10.1016/j.gendis.2020.05.007
Fu-Mei Duan , Li-Juan Fu , Yong-Heng Wang , Enoch Appiah Adu-Gyamfi , Ling- Ling Ruan , Zeng-Wei Xu , Shi-Quan Xiao , Xue-Mei Chen , Ying-Xiong Wang , Tai-Hang Liu , Yu-Bin Ding

Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses. It originates from abnormal placentation, especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast. In this study, we found that THBS1, a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions, is downregulated during the fusion of primary cytotrophoblast and BeWo cells, but upregulated in the placenta of pregnancies complicated by preeclampsia. Also, THBS1 was observed to interact with CD36, a membrane signal receptor and activator of the cAMP signaling pathway, to regulate the fusion of cytotrophoblast cells. Overexpression of THBS1 inhibited the cAMP signaling pathway and reduced the BeWo cells fusion ratio, while the effects of THBS1 were abolished by a CD36-blocking antibody. Our results suggest that THBS1 signals through a CD36-mediated cAMP pathway to regulate syncytialization of the cytotrophoblast cells, and that its upregulation impairs placental formation to cause preeclampsia. Thus, THBS1 can serve as a therapeutic target regarding the mitigation of abnormal syncytialization and preeclampsia.



中文翻译:

THBS1通过CD36依赖性抑制cAMP调节滋养细胞融合,其上调参与先兆子痫

子痫前期是妊娠并发症,它威胁母亲和胎儿的生存。它来自胎盘异常,尤其是滋养层细胞融合不足而形成合体滋养层。在这项研究中,我们发现THBS1是一种介导细胞与细胞和细胞与基质相互作用的基质细胞蛋白,在原代细胞滋养层细胞与BeWo细胞融合过程中被下调,但在妊娠合并先兆子痫的胎盘中被上调。同样,观察到THBS1与CD36(一种膜信号受体和cAMP信号传导途径的激活剂)相互作用,以调节细胞滋养层细胞的融合。THBS1的过表达抑制了cAMP信号通路并降低了BeWo细胞的融合率,而CD36阻断抗体则消除了THBS1的作用。我们的结果表明,THBS1通过CD36介导的cAMP信号通路来调节细胞滋养层细胞的合胞体化,并且其上调会损害胎盘的形成,从而导致先兆子痫。因此,THBS1可以作为缓解异常合胞和子痫前期的治疗靶标。

更新日期:2020-06-08
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