Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus
Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membran...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00236/full |
| _version_ | 1819116061786636288 |
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| author | Hana Park Hana Park Seo-Hyeon Choi Seo-Hyeon Choi Min-Jeong Kong Min-Jeong Kong Tae-Cheon Kang Tae-Cheon Kang |
| author_facet | Hana Park Hana Park Seo-Hyeon Choi Seo-Hyeon Choi Min-Jeong Kong Min-Jeong Kong Tae-Cheon Kang Tae-Cheon Kang |
| author_sort | Hana Park |
| collection | DOAJ |
| description | Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis. |
| first_indexed | 2024-12-22T05:11:06Z |
| format | Article |
| id | doaj.art-fcd17d2151d8442185eb66fe74b6610f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T05:11:06Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-fcd17d2151d8442185eb66fe74b6610f2022-12-21T18:37:58ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-05-011310.3389/fncel.2019.00236460442Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status EpilepticusHana Park0Hana Park1Seo-Hyeon Choi2Seo-Hyeon Choi3Min-Jeong Kong4Min-Jeong Kong5Tae-Cheon Kang6Tae-Cheon Kang7Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, South KoreaInstitute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, South KoreaDepartment of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, South KoreaInstitute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, South KoreaDepartment of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, South KoreaInstitute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, South KoreaDepartment of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, South KoreaInstitute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, South KoreaStatus epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis.https://www.frontiersin.org/article/10.3389/fncel.2019.00236/fullSMI-71eNOSSB202190lamininvasogenic edema |
| spellingShingle | Hana Park Hana Park Seo-Hyeon Choi Seo-Hyeon Choi Min-Jeong Kong Min-Jeong Kong Tae-Cheon Kang Tae-Cheon Kang Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus Frontiers in Cellular Neuroscience SMI-71 eNOS SB202190 laminin vasogenic edema |
| title | Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus |
| title_full | Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus |
| title_fullStr | Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus |
| title_full_unstemmed | Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus |
| title_short | Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus |
| title_sort | dysfunction of 67 kda laminin receptor disrupts bbb integrity via impaired dystrophin aqp4 complex and p38 mapk vegf activation following status epilepticus |
| topic | SMI-71 eNOS SB202190 laminin vasogenic edema |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00236/full |
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