Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction
Abstract Stroke is a multiphasic process involving a direct ischemic brain injury which is then exacerbated by the influx of immune cells into the brain tissue. Activation of brain endothelial cells leads to the expression of adhesion molecules such vascular cell adhesion molecule 1 (VCAM-1) on endo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84987-z |
| _version_ | 1818436039295893504 |
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| author | Lori N. Eidson Qingzeng Gao Hongyan Qu Daniel S. Kikuchi Ana Carolina P. Campos Elizabeth A. Faidley Yu-Yo Sun Chia-Yi Kuan Rosana L. Pagano Bernard Lassègue Malú G. Tansey Kathy K. Griendling Marina S. Hernandes |
| author_facet | Lori N. Eidson Qingzeng Gao Hongyan Qu Daniel S. Kikuchi Ana Carolina P. Campos Elizabeth A. Faidley Yu-Yo Sun Chia-Yi Kuan Rosana L. Pagano Bernard Lassègue Malú G. Tansey Kathy K. Griendling Marina S. Hernandes |
| author_sort | Lori N. Eidson |
| collection | DOAJ |
| description | Abstract Stroke is a multiphasic process involving a direct ischemic brain injury which is then exacerbated by the influx of immune cells into the brain tissue. Activation of brain endothelial cells leads to the expression of adhesion molecules such vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells, further increasing leukocyte recruitment. Polymerase δ-interacting protein 2 (Poldip2) promotes brain vascular inflammation and leukocyte recruitment via unknown mechanisms. This study aimed to define the role of Poldip2 in mediating vascular inflammation and leukocyte recruitment following cerebral ischemia. Cerebral ischemia was induced in Poldip2+/+ and Poldip2+/− mice and brains were isolated and processed for flow cytometry or RT-PCR. Cultured rat brain microvascular endothelial cells were used to investigate the effect of Poldip2 depletion on focal adhesion kinase (FAK)-mediated VCAM-1 induction. Poldip2 depletion in vivo attenuated the infiltration of myeloid cells, inflammatory monocytes/macrophages and decreased the induction of adhesion molecules. Focusing on VCAM-1, we demonstrated mechanistically that FAK activation was a critical intermediary in Poldip2-mediated VCAM-1 induction. In conclusion, Poldip2 is an important mediator of endothelial dysfunction and leukocyte recruitment. Thus, Poldip2 could be a therapeutic target to improve morbidity following ischemic stroke. |
| first_indexed | 2024-12-14T17:02:26Z |
| format | Article |
| id | doaj.art-ca6d527a5c274240a41e6c574dee592d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T17:02:26Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ca6d527a5c274240a41e6c574dee592d2022-12-21T22:53:49ZengNature PortfolioScientific Reports2045-23222021-03-0111111310.1038/s41598-021-84987-zPoldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 inductionLori N. Eidson0Qingzeng Gao1Hongyan Qu2Daniel S. Kikuchi3Ana Carolina P. Campos4Elizabeth A. Faidley5Yu-Yo Sun6Chia-Yi Kuan7Rosana L. Pagano8Bernard Lassègue9Malú G. Tansey10Kathy K. Griendling11Marina S. Hernandes12Department of Physiology, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDepartment of Neuroscience, University of VirginiaDepartment of Neuroscience, University of VirginiaDepartment of Neuroscience, Hospital Sírio-LibanêsDivision of Cardiology, Department of Medicine, Emory UniversityDepartment of Physiology, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityDivision of Cardiology, Department of Medicine, Emory UniversityAbstract Stroke is a multiphasic process involving a direct ischemic brain injury which is then exacerbated by the influx of immune cells into the brain tissue. Activation of brain endothelial cells leads to the expression of adhesion molecules such vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells, further increasing leukocyte recruitment. Polymerase δ-interacting protein 2 (Poldip2) promotes brain vascular inflammation and leukocyte recruitment via unknown mechanisms. This study aimed to define the role of Poldip2 in mediating vascular inflammation and leukocyte recruitment following cerebral ischemia. Cerebral ischemia was induced in Poldip2+/+ and Poldip2+/− mice and brains were isolated and processed for flow cytometry or RT-PCR. Cultured rat brain microvascular endothelial cells were used to investigate the effect of Poldip2 depletion on focal adhesion kinase (FAK)-mediated VCAM-1 induction. Poldip2 depletion in vivo attenuated the infiltration of myeloid cells, inflammatory monocytes/macrophages and decreased the induction of adhesion molecules. Focusing on VCAM-1, we demonstrated mechanistically that FAK activation was a critical intermediary in Poldip2-mediated VCAM-1 induction. In conclusion, Poldip2 is an important mediator of endothelial dysfunction and leukocyte recruitment. Thus, Poldip2 could be a therapeutic target to improve morbidity following ischemic stroke.https://doi.org/10.1038/s41598-021-84987-z |
| spellingShingle | Lori N. Eidson Qingzeng Gao Hongyan Qu Daniel S. Kikuchi Ana Carolina P. Campos Elizabeth A. Faidley Yu-Yo Sun Chia-Yi Kuan Rosana L. Pagano Bernard Lassègue Malú G. Tansey Kathy K. Griendling Marina S. Hernandes Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction Scientific Reports |
| title | Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction |
| title_full | Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction |
| title_fullStr | Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction |
| title_full_unstemmed | Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction |
| title_short | Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction |
| title_sort | poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase mediated vcam 1 induction |
| url | https://doi.org/10.1038/s41598-021-84987-z |
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