Axl deficiency promotes preeclampsia and vascular malformations in mice
Preeclampsia (PE) is a significant complication of pregnancy, occurring in approximately 10% of pregnancies. However, the underlying mechanisms of this condition remain unclear. Placentation and tumorigenesis both share many characteristics, but PE is the result of insufficient placentation, in cont...
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124002956 |
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| author | Chan Zhou Yunqing Zhu Liang Zhang Miaomiao Zhao Cong Zhang |
| author_facet | Chan Zhou Yunqing Zhu Liang Zhang Miaomiao Zhao Cong Zhang |
| author_sort | Chan Zhou |
| collection | DOAJ |
| description | Preeclampsia (PE) is a significant complication of pregnancy, occurring in approximately 10% of pregnancies. However, the underlying mechanisms of this condition remain unclear. Placentation and tumorigenesis both share many characteristics, but PE is the result of insufficient placentation, in contrast to the overaggression of tumorigenesis. AXL is a biomarker and therapeutic target for multiple metastatic cancers. We hypothesized that its downregulation could play a crucial role in the development of PE. In our study, we demonstrated that pregnant Axl−/− mice exhibited typical PE symptoms, such as hypertension, proteinuria, and inadequate trophoblast invasion and spiral artery remodeling. Cross-mating and embryo transplantation experiments confirmed that these phenotypes were caused by the decidua. RNA sequencing results revealed the abnormal expression of several transcripts in the decidua, including Corin, which encodes a cardiac protease responsible for activating atrial natriuretic peptide (ANP). ANP is a cardiac hormone that regulates sodium homeostasis and blood pressure. Chromatin immunoprecipitation-qPCR analysis indicated that the decreased CORIN in Axl−/− decidua was due to reduced signal transducer and activator of transcription 3 (STAT3) binding. Treatment with ANP successfully alleviated the PE symptoms. Furthermore, we observed that in PE decidua, the level of AXL was significantly lower compared to normal pregnancies. These findings suggest that the dysregulation of decidua-derived AXL-CORIN-ANP signaling disrupts maternal-fetal crosstalk and contributes to the development of PE. |
| format | Article |
| id | doaj-art-114269ae9e1e4d5c8d91c4569f3f9d0a |
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| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-114269ae9e1e4d5c8d91c4569f3f9d0a2025-08-20T02:38:05ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-0136110240810.1016/j.omtn.2024.102408Axl deficiency promotes preeclampsia and vascular malformations in miceChan Zhou0Yunqing Zhu1Liang Zhang2Miaomiao Zhao3Cong Zhang4Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China; Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, ChinaShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, ChinaResearch Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, ChinaShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, ChinaCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China; Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China; Corresponding author: Cong Zhang, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, ChinaPreeclampsia (PE) is a significant complication of pregnancy, occurring in approximately 10% of pregnancies. However, the underlying mechanisms of this condition remain unclear. Placentation and tumorigenesis both share many characteristics, but PE is the result of insufficient placentation, in contrast to the overaggression of tumorigenesis. AXL is a biomarker and therapeutic target for multiple metastatic cancers. We hypothesized that its downregulation could play a crucial role in the development of PE. In our study, we demonstrated that pregnant Axl−/− mice exhibited typical PE symptoms, such as hypertension, proteinuria, and inadequate trophoblast invasion and spiral artery remodeling. Cross-mating and embryo transplantation experiments confirmed that these phenotypes were caused by the decidua. RNA sequencing results revealed the abnormal expression of several transcripts in the decidua, including Corin, which encodes a cardiac protease responsible for activating atrial natriuretic peptide (ANP). ANP is a cardiac hormone that regulates sodium homeostasis and blood pressure. Chromatin immunoprecipitation-qPCR analysis indicated that the decreased CORIN in Axl−/− decidua was due to reduced signal transducer and activator of transcription 3 (STAT3) binding. Treatment with ANP successfully alleviated the PE symptoms. Furthermore, we observed that in PE decidua, the level of AXL was significantly lower compared to normal pregnancies. These findings suggest that the dysregulation of decidua-derived AXL-CORIN-ANP signaling disrupts maternal-fetal crosstalk and contributes to the development of PE.http://www.sciencedirect.com/science/article/pii/S2162253124002956MT: RNA/DNA EditingANPAXLCORINDeciduaPlacenta |
| spellingShingle | Chan Zhou Yunqing Zhu Liang Zhang Miaomiao Zhao Cong Zhang Axl deficiency promotes preeclampsia and vascular malformations in mice Molecular Therapy: Nucleic Acids MT: RNA/DNA Editing ANP AXL CORIN Decidua Placenta |
| title | Axl deficiency promotes preeclampsia and vascular malformations in mice |
| title_full | Axl deficiency promotes preeclampsia and vascular malformations in mice |
| title_fullStr | Axl deficiency promotes preeclampsia and vascular malformations in mice |
| title_full_unstemmed | Axl deficiency promotes preeclampsia and vascular malformations in mice |
| title_short | Axl deficiency promotes preeclampsia and vascular malformations in mice |
| title_sort | axl deficiency promotes preeclampsia and vascular malformations in mice |
| topic | MT: RNA/DNA Editing ANP AXL CORIN Decidua Placenta |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124002956 |
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