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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca6d527a5c274240a41e6c574dee592d
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spelling	oai:doaj.org-article:ca6d527a5c274240a41e6c574dee592d2021-12-02T13:35:05ZPoldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction10.1038/s41598-021-84987-z2045-2322https://doaj.org/article/ca6d527a5c274240a41e6c574dee592d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84987-zhttps://doaj.org/toc/2045-2322Abstract 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.Lori N. EidsonQingzeng GaoHongyan QuDaniel S. KikuchiAna Carolina P. CamposElizabeth A. FaidleyYu-Yo SunChia-Yi KuanRosana L. PaganoBernard LassègueMalú G. TanseyKathy K. GriendlingMarina S. HernandesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated vcam-1 induction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca6d527a5c274240a41e6c574dee592d
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Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction

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