THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP,and its upregulation participates in preeclampsia

作     者：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 

作者机构：School of Public Health and ManagementChongqing Medical UniversityChongqing400016PR China Department of BioinformaticsThe School of Basic MedicineChongqing Medical UniversityChongqing400016PR China The Joint International Research Laboratory of Reproduction and DevelopmentMinistry of EducationChongqing400016PR China Department of Herbal MedicineSchool of Traditional Chinese MedicineChongqing Medical UniversityChongqing400016PR China Department of Reproductive MedicineThe Third Affiliated HospitalChongqing Medical UniversityChongqing401120PR China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2021年第8卷第3期

页      面：353-363页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100211[医学-妇产科学] 0703[理学-化学] 10[医学] 

基　　金：This work was funded by the National Natural Science Foundation of China:[grant numbers 81671493,81801458] Chongqing Science and Technology Commission[grant number cstc2017jcyJAX0410]. 

主　　题：cAMP Cell fusion Preeclampsia THBS1 Trophoblast 

摘      要：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.