PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation
Abstract Maternal immune activation (MIA) is recognised as a risk factor in the neurodevelopmental disorders. However, the precise molecular pathways through which MIA disrupts neurovascular function remain largely unexplored. Here, we identify a novel MIA‐associated brain endothelial piRNA (MIABEPI...
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| Format: | Article |
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Wiley
2025-03-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70260 |
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| author | Shan‐Shan Li Miao Guo Yao Long Yuang Cai Ying Zhao Shaoyuan Huang Houzhi Yang Yonggang Fan Xu Chen Xin Jin |
| author_facet | Shan‐Shan Li Miao Guo Yao Long Yuang Cai Ying Zhao Shaoyuan Huang Houzhi Yang Yonggang Fan Xu Chen Xin Jin |
| author_sort | Shan‐Shan Li |
| collection | DOAJ |
| description | Abstract Maternal immune activation (MIA) is recognised as a risk factor in the neurodevelopmental disorders. However, the precise molecular pathways through which MIA disrupts neurovascular function remain largely unexplored. Here, we identify a novel MIA‐associated brain endothelial piRNA (MIABEPIR) involved in regulating BMEC function and BBB integrity. RNA microarray analysis of foetal brain tissue from MIA‐exposed mice revealed significant changes in piRNA expression, including a marked upregulation of MIABEPIR upregulated piRNAs. Immunofluorescence and FISH confirmed that MIABEPIR is localised in the microvascular endothelial cells of the brain. MIABEPIR overexpression enhances BMEC proliferation and angiogenesis but disrupts BBB integrity. In vivo, intracranial administration of lentiviral MIABEPIR in foetal mice resulted in marked BBB disruption. Mechanistically, we identified DAPK2 as a downstream target of MIABEPIR, leading to its downregulation. This suppression of DAPK2 inhibits autophagy in BMECs, suggesting that MIABEPIR modulates endothelial cell autophagy through the DAPK2 pathway. Our findings reveal a novel piRNA‐mediated regulatory mechanism in neurovascular function during MIA and highlight MIABEPIR's role in MIA‐induced neurodevelopmental abnormalities. Targeting the MIABEPIR‐DAPK2 axis represents a potential therapeutic strategy for addressing neurovascular dysfunction in neurodevelopmental disorders associated with maternal immune stress. |
| format | Article |
| id | doaj-art-434ba2f66b524cafa3ee73145f9011eb |
| institution | OA Journals |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj-art-434ba2f66b524cafa3ee73145f9011eb2025-08-20T01:52:18ZengWileyClinical and Translational Medicine2001-13262025-03-01153n/an/a10.1002/ctm2.70260PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activationShan‐Shan Li0Miao Guo1Yao Long2Yuang Cai3Ying Zhao4Shaoyuan Huang5Houzhi Yang6Yonggang Fan7Xu Chen8Xin Jin9School of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaTianjin Medical University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaSchool of Medicine Nankai University Tianjin ChinaAbstract Maternal immune activation (MIA) is recognised as a risk factor in the neurodevelopmental disorders. However, the precise molecular pathways through which MIA disrupts neurovascular function remain largely unexplored. Here, we identify a novel MIA‐associated brain endothelial piRNA (MIABEPIR) involved in regulating BMEC function and BBB integrity. RNA microarray analysis of foetal brain tissue from MIA‐exposed mice revealed significant changes in piRNA expression, including a marked upregulation of MIABEPIR upregulated piRNAs. Immunofluorescence and FISH confirmed that MIABEPIR is localised in the microvascular endothelial cells of the brain. MIABEPIR overexpression enhances BMEC proliferation and angiogenesis but disrupts BBB integrity. In vivo, intracranial administration of lentiviral MIABEPIR in foetal mice resulted in marked BBB disruption. Mechanistically, we identified DAPK2 as a downstream target of MIABEPIR, leading to its downregulation. This suppression of DAPK2 inhibits autophagy in BMECs, suggesting that MIABEPIR modulates endothelial cell autophagy through the DAPK2 pathway. Our findings reveal a novel piRNA‐mediated regulatory mechanism in neurovascular function during MIA and highlight MIABEPIR's role in MIA‐induced neurodevelopmental abnormalities. Targeting the MIABEPIR‐DAPK2 axis represents a potential therapeutic strategy for addressing neurovascular dysfunction in neurodevelopmental disorders associated with maternal immune stress.https://doi.org/10.1002/ctm2.70260autophagyblood–brain barrierbrain microvascular endothelial cellmaternal immune activationPIWI‐interacting RNA |
| spellingShingle | Shan‐Shan Li Miao Guo Yao Long Yuang Cai Ying Zhao Shaoyuan Huang Houzhi Yang Yonggang Fan Xu Chen Xin Jin PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation Clinical and Translational Medicine autophagy blood–brain barrier brain microvascular endothelial cell maternal immune activation PIWI‐interacting RNA |
| title | PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation |
| title_full | PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation |
| title_fullStr | PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation |
| title_full_unstemmed | PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation |
| title_short | PIWI‐interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation |
| title_sort | piwi interacting rna miabepir regulates cerebral endothelial cell function via dapk2 pathway in offspring following maternal immune activation |
| topic | autophagy blood–brain barrier brain microvascular endothelial cell maternal immune activation PIWI‐interacting RNA |
| url | https://doi.org/10.1002/ctm2.70260 |
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