STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia
ObjectivesAbnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown....
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.615973/full |
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| author | Yan Li Xian-li Sun Chun-ling Ma Chao Li Ying Zhan Wen-ting Li Can Li Yi-hao Wang |
| author_facet | Yan Li Xian-li Sun Chun-ling Ma Chao Li Ying Zhan Wen-ting Li Can Li Yi-hao Wang |
| author_sort | Yan Li |
| collection | DOAJ |
| description | ObjectivesAbnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown. The aim of this study was to explore the role of STX2 on trophoblast biology and unravel the molecular mechanisms that contribute to the development and progression of PE.Materials and MethodsWe first compared the expression of STX2 in placental tissues from women with PE and women with normal pregnancies. Then, we investigated the role of STX2 on trophoblast proliferation, migration and invasion in HTR-8/SVneo and primary human trophoblast cells by loss or gain of function experiments. In addition, co-immunoprecipitation, pulldown and immunofluorescence assays were performed to investigate the co-localization of STX2 with other proteins, and to help clarify the mechanisms underlying STX2-mediated functions on trophoblasts.ResultsWe demonstrated that STX2 expression was downregulated in placental tissues of women with PE compared with those from normal pregnancies. Loss and gain of function experiments further confirmed a role for STX2 in cell proliferation, migration and invasion in trophoblasts. By co-immunoprecipitation, pulldown and immunofluorescence co-localization assays, we revealed that STX2 selectively interacted with p85, a subunit of PI3K, and directly recruited p85 to the cytomembrane, thereby activating the AKT signaling pathway. We further demonstrated that the AKT activation was abolished by the use of a PI3K inhibitor (LY294002), which negatively affected STX2-mediated functions on trophoblasts.ConclusionAll together, our findings point to a crucial role for STX2 in PE progression. Our new insights also suggest that STX2 may be a potential diagnostic tool and a novel therapeutic target for treating PE. |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-18T01:47:05Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f3e67b56b0a2452fa7ae916a44d4dd5d2022-12-21T21:25:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.615973615973STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in PreeclampsiaYan Li0Xian-li Sun1Chun-ling Ma2Chao Li3Ying Zhan4Wen-ting Li5Can Li6Yi-hao Wang7Department of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynecology, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Pain Management, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaObjectivesAbnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown. The aim of this study was to explore the role of STX2 on trophoblast biology and unravel the molecular mechanisms that contribute to the development and progression of PE.Materials and MethodsWe first compared the expression of STX2 in placental tissues from women with PE and women with normal pregnancies. Then, we investigated the role of STX2 on trophoblast proliferation, migration and invasion in HTR-8/SVneo and primary human trophoblast cells by loss or gain of function experiments. In addition, co-immunoprecipitation, pulldown and immunofluorescence assays were performed to investigate the co-localization of STX2 with other proteins, and to help clarify the mechanisms underlying STX2-mediated functions on trophoblasts.ResultsWe demonstrated that STX2 expression was downregulated in placental tissues of women with PE compared with those from normal pregnancies. Loss and gain of function experiments further confirmed a role for STX2 in cell proliferation, migration and invasion in trophoblasts. By co-immunoprecipitation, pulldown and immunofluorescence co-localization assays, we revealed that STX2 selectively interacted with p85, a subunit of PI3K, and directly recruited p85 to the cytomembrane, thereby activating the AKT signaling pathway. We further demonstrated that the AKT activation was abolished by the use of a PI3K inhibitor (LY294002), which negatively affected STX2-mediated functions on trophoblasts.ConclusionAll together, our findings point to a crucial role for STX2 in PE progression. Our new insights also suggest that STX2 may be a potential diagnostic tool and a novel therapeutic target for treating PE.https://www.frontiersin.org/articles/10.3389/fcell.2021.615973/fullsyntaxin2trophoblastPI3KAKTpreeclampsia |
| spellingShingle | Yan Li Xian-li Sun Chun-ling Ma Chao Li Ying Zhan Wen-ting Li Can Li Yi-hao Wang STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia Frontiers in Cell and Developmental Biology syntaxin2 trophoblast PI3K AKT preeclampsia |
| title | STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia |
| title_full | STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia |
| title_fullStr | STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia |
| title_full_unstemmed | STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia |
| title_short | STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia |
| title_sort | stx2 promotes trophoblast growth migration and invasion through activation of the pi3k akt pathway in preeclampsia |
| topic | syntaxin2 trophoblast PI3K AKT preeclampsia |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.615973/full |
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