THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia
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 mediat...
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KeAi Communications Co., Ltd.
2021-05-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300726 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fu-Mei Duan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T08:33:45Z |
| format | Article |
| id | doaj.art-5a166452b85945d7ba6b5d35f787c077 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T08:33:45Z |
| publishDate | 2021-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-5a166452b85945d7ba6b5d35f787c0772023-09-02T17:25:37ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422021-05-0183353363THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsiaFu-Mei Duan0Li-Juan Fu1Yong-Heng Wang2Enoch Appiah Adu-Gyamfi3Ling- Ling Ruan4Zeng-Wei Xu5Shi-Quan Xiao6Xue-Mei Chen7Ying-Xiong Wang8Tai-Hang Liu9Yu-Bin Ding10School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR ChinaDepartment of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, PR ChinaThe Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR ChinaThe Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR ChinaDepartment of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, PR ChinaSchool of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR ChinaThe Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR China; Department of Reproductive Medicine, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 401120, PR ChinaSchool of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR China; The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR ChinaSchool of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR China; The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR ChinaDepartment of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR China; The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR China; Corresponding author. Box 197, Chongqing Medical University, No.1 Yixueyuan Rd, Chongqing, 400016, PR China. Tel.: +86 023 68485008; fax: +86 23 68485000.School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR China; The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, 400016, PR China; Corresponding author. Box 197, Chongqing Medical University, No.1 Yixueyuan Rd, Chongqing, 400016, PR China. Tel.: +86 023 68485008; fax: +86 23 68485000.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.http://www.sciencedirect.com/science/article/pii/S2352304220300726cAMPCell fusionPreeclampsiaTHBS1Trophoblast |
| spellingShingle | 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 THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia Genes and Diseases cAMP Cell fusion Preeclampsia THBS1 Trophoblast |
| title | THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia |
| title_full | THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia |
| title_fullStr | THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia |
| title_full_unstemmed | THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia |
| title_short | THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia |
| title_sort | thbs1 regulates trophoblast fusion through a cd36 dependent inhibition of camp and its upregulation participates in preeclampsia |
| topic | cAMP Cell fusion Preeclampsia THBS1 Trophoblast |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300726 |
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