Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis
BackgroundBlood–brain barrier (BBB) disruption aggravates brain injury induced by intracerebral hemorrhage (ICH); however, the mechanisms of BBB damage caused by ICH remain elusive. Mfsd2a (major facilitator superfamily domain containing 2a) has been known to play an essential role in BBB formation...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.005811 |
| _version_ | 1818315096866160640 |
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| author | Yuan‐Rui Yang Xiao‐Yi Xiong Juan Liu Li‐Rong Wu Qi Zhong Kai Zhou Zhao‐You Meng Liang Liu Fa‐Xiang Wang Qiu‐Wen Gong Mao‐Fan Liao Chun‐Mei Duan Jie Li Mei‐Hua Yang Qin Zhang Chang‐Xiong Gong Qing‐Wu Yang |
| author_facet | Yuan‐Rui Yang Xiao‐Yi Xiong Juan Liu Li‐Rong Wu Qi Zhong Kai Zhou Zhao‐You Meng Liang Liu Fa‐Xiang Wang Qiu‐Wen Gong Mao‐Fan Liao Chun‐Mei Duan Jie Li Mei‐Hua Yang Qin Zhang Chang‐Xiong Gong Qing‐Wu Yang |
| author_sort | Yuan‐Rui Yang |
| collection | DOAJ |
| description | BackgroundBlood–brain barrier (BBB) disruption aggravates brain injury induced by intracerebral hemorrhage (ICH); however, the mechanisms of BBB damage caused by ICH remain elusive. Mfsd2a (major facilitator superfamily domain containing 2a) has been known to play an essential role in BBB formation and function. In this study, we investigated the role and underlying mechanisms of Mfsd2a in BBB permeability regulation after ICH. Methods and ResultsUsing ICH models, we found that Mfsd2a protein expression in perihematomal brain tissues was significantly decreased after ICH. Knockdown and knockout of Mfsd2a in mice markedly increased BBB permeability, neurological deficit score, and brain water contents after ICH, and these were rescued by overexpressing Mfsd2a in perihematomas. Moreover, we found that Mfsd2a regulation of BBB permeability after ICH correlated with changes in vesicle number. Expression profiling of tight junction proteins showed no differences in Mfsd2a knockdown, Mfsd2a knockout, and Mfsd2a overexpression mice. However, using electron microscopy following ICH, we observed a significant increase in pinocytotic vesicle number in Mfsd2a knockout mice and decreased the number of pinocytotic vesicles in mouse brains with Mfsd2a overexpression. Finally, using multiple reaction monitoring, we screened out 3 vesicle trafficking–related proteins (Srgap2, Stx7, and Sec22b) from 31 vesicle trafficking‐related proteins that were markedly upregulated in Mfsd2a knockout mice compared with controls after ICH. ConclusionsIn summary, our results suggest that Mfsd2a may protect against BBB injury by inhibiting vesicular transcytosis following ICH. |
| first_indexed | 2024-12-13T09:00:06Z |
| format | Article |
| id | doaj.art-29319a75f4504e3fa79d4361d7d1f108 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-13T09:00:06Z |
| publishDate | 2017-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-29319a75f4504e3fa79d4361d7d1f1082022-12-21T23:53:11ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-07-016710.1161/JAHA.117.005811Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular TranscytosisYuan‐Rui Yang0Xiao‐Yi Xiong1Juan Liu2Li‐Rong Wu3Qi Zhong4Kai Zhou5Zhao‐You Meng6Liang Liu7Fa‐Xiang Wang8Qiu‐Wen Gong9Mao‐Fan Liao10Chun‐Mei Duan11Jie Li12Mei‐Hua Yang13Qin Zhang14Chang‐Xiong Gong15Qing‐Wu Yang16Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaBackgroundBlood–brain barrier (BBB) disruption aggravates brain injury induced by intracerebral hemorrhage (ICH); however, the mechanisms of BBB damage caused by ICH remain elusive. Mfsd2a (major facilitator superfamily domain containing 2a) has been known to play an essential role in BBB formation and function. In this study, we investigated the role and underlying mechanisms of Mfsd2a in BBB permeability regulation after ICH. Methods and ResultsUsing ICH models, we found that Mfsd2a protein expression in perihematomal brain tissues was significantly decreased after ICH. Knockdown and knockout of Mfsd2a in mice markedly increased BBB permeability, neurological deficit score, and brain water contents after ICH, and these were rescued by overexpressing Mfsd2a in perihematomas. Moreover, we found that Mfsd2a regulation of BBB permeability after ICH correlated with changes in vesicle number. Expression profiling of tight junction proteins showed no differences in Mfsd2a knockdown, Mfsd2a knockout, and Mfsd2a overexpression mice. However, using electron microscopy following ICH, we observed a significant increase in pinocytotic vesicle number in Mfsd2a knockout mice and decreased the number of pinocytotic vesicles in mouse brains with Mfsd2a overexpression. Finally, using multiple reaction monitoring, we screened out 3 vesicle trafficking–related proteins (Srgap2, Stx7, and Sec22b) from 31 vesicle trafficking‐related proteins that were markedly upregulated in Mfsd2a knockout mice compared with controls after ICH. ConclusionsIn summary, our results suggest that Mfsd2a may protect against BBB injury by inhibiting vesicular transcytosis following ICH.https://www.ahajournals.org/doi/10.1161/JAHA.117.005811blood–brain barrierintracerebral hemorrhageMfsd2avesicular transcytosis |
| spellingShingle | Yuan‐Rui Yang Xiao‐Yi Xiong Juan Liu Li‐Rong Wu Qi Zhong Kai Zhou Zhao‐You Meng Liang Liu Fa‐Xiang Wang Qiu‐Wen Gong Mao‐Fan Liao Chun‐Mei Duan Jie Li Mei‐Hua Yang Qin Zhang Chang‐Xiong Gong Qing‐Wu Yang Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease blood–brain barrier intracerebral hemorrhage Mfsd2a vesicular transcytosis |
| title | Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis |
| title_full | Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis |
| title_fullStr | Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis |
| title_full_unstemmed | Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis |
| title_short | Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage–Induced Blood–Brain Barrier Disruption by Inhibiting Vesicular Transcytosis |
| title_sort | mfsd2a major facilitator superfamily domain containing 2a attenuates intracerebral hemorrhage induced blood brain barrier disruption by inhibiting vesicular transcytosis |
| topic | blood–brain barrier intracerebral hemorrhage Mfsd2a vesicular transcytosis |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.005811 |
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