ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression
Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a d...
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/101236 |
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| author | Shujing Yang Huanyao Liu Jieshi Hu Binjun Chen Wanlu An Xuwen Song Yi Yang Fang He |
| author_facet | Shujing Yang Huanyao Liu Jieshi Hu Binjun Chen Wanlu An Xuwen Song Yi Yang Fang He |
| author_sort | Shujing Yang |
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| description | Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8/SVneo and JAR cell lines. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in genome-wide association study. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare. |
| format | Article |
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| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-82c412f20efa4af6acf2e903dfc3c00f2025-08-20T03:21:55ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011410.7554/eLife.101236ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progressionShujing Yang0Huanyao Liu1Jieshi Hu2Binjun Chen3Wanlu An4Xuwen Song5Yi Yang6Fang He7https://orcid.org/0000-0003-3362-6002Department of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaPre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8/SVneo and JAR cell lines. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in genome-wide association study. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare.https://elifesciences.org/articles/101236pre-eclampsiaACVR2AHTR8/SVneoJARTCF7c-JUN |
| spellingShingle | Shujing Yang Huanyao Liu Jieshi Hu Binjun Chen Wanlu An Xuwen Song Yi Yang Fang He ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression eLife pre-eclampsia ACVR2A HTR8/SVneo JAR TCF7 c-JUN |
| title | ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression |
| title_full | ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression |
| title_fullStr | ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression |
| title_full_unstemmed | ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression |
| title_short | ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression |
| title_sort | acvr2a facilitates trophoblast cell invasion through tcf7 c jun pathway in pre eclampsia progression |
| topic | pre-eclampsia ACVR2A HTR8/SVneo JAR TCF7 c-JUN |
| url | https://elifesciences.org/articles/101236 |
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