Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease
Abstract Epidemiological studies show an association between inflammatory bowel disease (IBD) and increased risk of thrombosis. However, how IBD influences thrombosis remains unknown. The current study shows that formation of neutrophil extracellular traps (NETs) significantly increased in the dextr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202300560 |
| _version_ | 1827797344116015104 |
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| author | Long Zhang Bin Zheng Yang Bai Jing Zhou Xin‐hua Zhang Yu‐qin Yang Jing Yu Hong‐ye Zhao Dong Ma Han Wu Jin‐kun Wen |
| author_facet | Long Zhang Bin Zheng Yang Bai Jing Zhou Xin‐hua Zhang Yu‐qin Yang Jing Yu Hong‐ye Zhao Dong Ma Han Wu Jin‐kun Wen |
| author_sort | Long Zhang |
| collection | DOAJ |
| description | Abstract Epidemiological studies show an association between inflammatory bowel disease (IBD) and increased risk of thrombosis. However, how IBD influences thrombosis remains unknown. The current study shows that formation of neutrophil extracellular traps (NETs) significantly increased in the dextran sulfate sodium (DSS)‐induced IBD mice, which in turn, contributes to thrombus formation in a NETs‐dependent fashion. Furthermore, the exosomes isolated from the plasma of the IBD mice induce arterial and venous thrombosis in vivo. Importantly, proinflammatory factors‐exposed intestinal epithelial cells (inflamed IECs) promote neutrophils to release NETs through their secreted exosomes. RNA sequencing revealed that LINC00668 is highly enriched in the inflamed IECs‐derived exosomes. Mechanistically, LINC00668 facilitates the translocation of neutrophil elastase (NE) from the cytoplasmic granules to the nucleus via its interaction with NE in a sequence‐specific manner, thereby inducing NETs release and thrombus formation. Importantly, berberine (BBR) suppresses the nuclear translocation of NE and subsequent NETs formation by inhibiting the interaction of LINC00668 with NE, thus exerting its antithrombotic effects. This study provides a novel pathobiological mechanism linking IBD and thrombosis by exosome‐mediated NETs formation. Targeting LINC00668 can serve as a novel molecular treatment strategy to treat IBD‐related thrombosis. |
| first_indexed | 2024-03-11T19:21:54Z |
| format | Article |
| id | doaj.art-365afb0c0b06413eb0d6bdc7cedf6c51 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T19:21:54Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-365afb0c0b06413eb0d6bdc7cedf6c512023-10-07T03:51:50ZengWileyAdvanced Science2198-38442023-10-011028n/an/a10.1002/advs.202300560Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel DiseaseLong Zhang0Bin Zheng1Yang Bai2Jing Zhou3Xin‐hua Zhang4Yu‐qin Yang5Jing Yu6Hong‐ye Zhao7Dong Ma8Han Wu9Jin‐kun Wen10Department of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Endocrine The Second Hospital of Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Respiratory The Second Hospital of Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaDepartment of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education of China Hebei Medical University Shijiazhuang 050017 ChinaAbstract Epidemiological studies show an association between inflammatory bowel disease (IBD) and increased risk of thrombosis. However, how IBD influences thrombosis remains unknown. The current study shows that formation of neutrophil extracellular traps (NETs) significantly increased in the dextran sulfate sodium (DSS)‐induced IBD mice, which in turn, contributes to thrombus formation in a NETs‐dependent fashion. Furthermore, the exosomes isolated from the plasma of the IBD mice induce arterial and venous thrombosis in vivo. Importantly, proinflammatory factors‐exposed intestinal epithelial cells (inflamed IECs) promote neutrophils to release NETs through their secreted exosomes. RNA sequencing revealed that LINC00668 is highly enriched in the inflamed IECs‐derived exosomes. Mechanistically, LINC00668 facilitates the translocation of neutrophil elastase (NE) from the cytoplasmic granules to the nucleus via its interaction with NE in a sequence‐specific manner, thereby inducing NETs release and thrombus formation. Importantly, berberine (BBR) suppresses the nuclear translocation of NE and subsequent NETs formation by inhibiting the interaction of LINC00668 with NE, thus exerting its antithrombotic effects. This study provides a novel pathobiological mechanism linking IBD and thrombosis by exosome‐mediated NETs formation. Targeting LINC00668 can serve as a novel molecular treatment strategy to treat IBD‐related thrombosis.https://doi.org/10.1002/advs.202300560berberinesexosomesinflammatory bowel diseasesLINC00668neutrophil elastaseneutrophil extracellular traps |
| spellingShingle | Long Zhang Bin Zheng Yang Bai Jing Zhou Xin‐hua Zhang Yu‐qin Yang Jing Yu Hong‐ye Zhao Dong Ma Han Wu Jin‐kun Wen Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease Advanced Science berberines exosomes inflammatory bowel diseases LINC00668 neutrophil elastase neutrophil extracellular traps |
| title | Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease |
| title_full | Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease |
| title_fullStr | Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease |
| title_full_unstemmed | Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease |
| title_short | Exosomes‐transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease |
| title_sort | exosomes transferred linc00668 contributes to thrombosis by promoting nets formation in inflammatory bowel disease |
| topic | berberines exosomes inflammatory bowel diseases LINC00668 neutrophil elastase neutrophil extracellular traps |
| url | https://doi.org/10.1002/advs.202300560 |
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