Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases
Abstract Ischemic injury induces a partial mesenchymal shift in endothelial cells (ECs), contributing to impaired vascular regeneration. However, the molecular regulators of this transitional state remain poorly defined. To address this, we performed circular RNA profiling of endothelial cells under...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61596-2 |
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| author | Yue Li Zhe Zheng Yanze Li Siyuan Fan Lingyao Kong Wanrong Fu Zhonggen Li Jianchao Zhang Shuang Li Zongtao Liu Chao Liu Jinhua Cao Zhenxuan Hao Lili Xiao Youyou Du Xiaofang Wang Lu Gao |
| author_facet | Yue Li Zhe Zheng Yanze Li Siyuan Fan Lingyao Kong Wanrong Fu Zhonggen Li Jianchao Zhang Shuang Li Zongtao Liu Chao Liu Jinhua Cao Zhenxuan Hao Lili Xiao Youyou Du Xiaofang Wang Lu Gao |
| author_sort | Yue Li |
| collection | DOAJ |
| description | Abstract Ischemic injury induces a partial mesenchymal shift in endothelial cells (ECs), contributing to impaired vascular regeneration. However, the molecular regulators of this transitional state remain poorly defined. To address this, we performed circular RNA profiling of endothelial cells under ischemic-like conditions and identified a marked upregulation of a circular RNA, named circATXN1. Functional studies revealed that circATXN1 knockdown modulates endothelial phenotype and vascular response after ischemia. Functional studies have shown that knockdown of circATXN1 can regulate the endothelial cell phenotype and vascular response after ischemia. Mechanistically, circATXN1 knockdown enhances the demethylase protein ALKBH5 to reduce the RNA methylation level of the key transcription factor SLUG, thereby stabilizing SLUG. In animal models, suppression of circATXN1 enhances angiogenesis and improves recovery following ischemic injury. Here, we show that circATXN1 regulates partial endothelial-to-mesenchymal transition (EndMT) and angiogenesis by controlling SLUG mRNA methylation dynamics, highlighting its potential as a therapeutic target in ischemic disease. |
| format | Article |
| id | doaj-art-94baec22a53f49a4abf7edf3b455b5df |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-94baec22a53f49a4abf7edf3b455b5df2025-08-20T04:03:06ZengNature PortfolioNature Communications2041-17232025-07-0116112010.1038/s41467-025-61596-2Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseasesYue Li0Zhe Zheng1Yanze Li2Siyuan Fan3Lingyao Kong4Wanrong Fu5Zhonggen Li6Jianchao Zhang7Shuang Li8Zongtao Liu9Chao Liu10Jinhua Cao11Zhenxuan Hao12Lili Xiao13Youyou Du14Xiaofang Wang15Lu Gao16Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Radiation Oncology Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityAbstract Ischemic injury induces a partial mesenchymal shift in endothelial cells (ECs), contributing to impaired vascular regeneration. However, the molecular regulators of this transitional state remain poorly defined. To address this, we performed circular RNA profiling of endothelial cells under ischemic-like conditions and identified a marked upregulation of a circular RNA, named circATXN1. Functional studies revealed that circATXN1 knockdown modulates endothelial phenotype and vascular response after ischemia. Functional studies have shown that knockdown of circATXN1 can regulate the endothelial cell phenotype and vascular response after ischemia. Mechanistically, circATXN1 knockdown enhances the demethylase protein ALKBH5 to reduce the RNA methylation level of the key transcription factor SLUG, thereby stabilizing SLUG. In animal models, suppression of circATXN1 enhances angiogenesis and improves recovery following ischemic injury. Here, we show that circATXN1 regulates partial endothelial-to-mesenchymal transition (EndMT) and angiogenesis by controlling SLUG mRNA methylation dynamics, highlighting its potential as a therapeutic target in ischemic disease.https://doi.org/10.1038/s41467-025-61596-2 |
| spellingShingle | Yue Li Zhe Zheng Yanze Li Siyuan Fan Lingyao Kong Wanrong Fu Zhonggen Li Jianchao Zhang Shuang Li Zongtao Liu Chao Liu Jinhua Cao Zhenxuan Hao Lili Xiao Youyou Du Xiaofang Wang Lu Gao Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases Nature Communications |
| title | Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases |
| title_full | Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases |
| title_fullStr | Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases |
| title_full_unstemmed | Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases |
| title_short | Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases |
| title_sort | regulation of partial endothelial to mesenchymal transition by circatxn1 in ischemic diseases |
| url | https://doi.org/10.1038/s41467-025-61596-2 |
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