THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia.
THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia.
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THBS1 通过 CD36 依赖性 cAMP 抑制来调节滋养层融合，其上调参与先兆子痫
DOI：
10.1016/j.gendis.2020.05.007
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发表时间：
2021-05
期刊：
影响因子：
6.8
通讯作者：
Ding YB
中科院分区：
文献类型：
--
作者：
Duan FM;Fu LJ;Wang YH;Adu-Gyamfi EA;Ruan LL;Xu ZW;Xiao SQ;Chen XM;Wang YX;Liu TH;Ding YB
先兆子痫是一种妊娠并发症，威胁母亲和胎儿的生存。它起源于异常的胎盘形成，特别是细胞滋养层细胞融合不充分形成合体滋养层。在这项研究中，我们发现，THBS1，一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和BeWo细胞融合过程中下调，但在先兆子痫并发的胎盘中上调。此外，THBS1被观察到与CD36，膜信号受体和cAMP信号通路的激活剂，相互作用，以调节细胞滋养层细胞的融合。过表达THBS1可抑制cAMP信号通路，降低BeWo细胞融合率，而CD36阻断抗体可阻断THBS1的作用。我们的研究结果表明，THBS1信号通过CD36介导的cAMP途径调节细胞滋养层细胞的合胞化，其上调损害胎盘形成，导致先兆子痫。因此，THBS1可以作为缓解异常合胞化和先兆子痫的治疗靶点。
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.
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DOI：
10.1083/jcb.138.3.707
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dawson DW;Pearce SF;Zhong R;Silverstein RL;Frazier WA;Bouck NP
通讯作者：
Bouck NP
影响因子：
20.1
作者：
Hung, TH;Skepper, JN;Burton, GJ
通讯作者：
Burton, GJ
影响因子：
3.8
作者：
Goswami, D;Tannetta, DS;von Dadelszen, P
通讯作者：
von Dadelszen, P
影响因子：
9.8
作者：
Bombrys, Annette E.;Barton, John R.;Sibai, Baha M.
通讯作者：
Sibai, Baha M.
影响因子：
4.8
作者：
Bein, K;Simons, M
通讯作者：
Simons, M