α2-adrenoreceptor modulated FAK pathway induced by dexmedetomidine attenuates pulmonary microvascular hyper-permeability following kidney injury

File Description SizeFormat 
10809-164144-3-PB.pdfPublished version1.74 MBAdobe PDFDownload
Title: α2-adrenoreceptor modulated FAK pathway induced by dexmedetomidine attenuates pulmonary microvascular hyper-permeability following kidney injury
Author(s): Chen, Q
Yi, B
Ma, J
Ning, J
Wu, L
Ma, D
Lu, K
Gu, J
Item Type: Journal Article
Abstract: Renal ischemia-reperfusion (rI/R) could cause remote acute lung injury (ALI) and combination of these two organ injuries can remarkably increase the mortality. This study aims to determine whether dexmedetomidine, an α2-adrenoreceptor agonist sedative, can ameliorate pulmonary microvascular hyper-permeability following rI/R injury and explore the underlying mechanisms. In vivo, C57BL/6J mice received dexmedetomidine (25µg/kg, i.p.) in the absence or presence of α2-adrenergic antagonist atipamezole (250µg/kg, i.p.) or focal adhesion kinase (FAK) inhibitor (30mg/kg, i.p.) before bilateral renal pedicle clamping for 45 minutes followed by 24 hours reperfusion. The lung histopathological changes and the permeability of pulmonary microvascular were assessed respectively. In vitro, the cultured C57BL/6J mice pulmonary microvascular endothelial cells (PMVECs) were treated with serum from mice with rI/R with or without dexmedetomidine and atipamezole. Trans-endothelial permeability and phospho-tyrosine397FAK, F-actin, VE-cadherin and ZO-1 in monolayer PMVECs were measured respectively in the presence or absence of rI/R serum, dexmedetomidine and FAK inhibitor. In vivo, dexmedetomidine remarkably attenuated lung injury and pulmonary microvascular hyper-permeability caused by rI/R injury, which was abolished by atipamezole or FAK inhibitor co-administration. In vitro, the permeability of PMVECs monolayer following exposure to serum from rI/R mice was increased significantly, and decreased by dexmedetomidine. Dexmedetomidine increased phospho-tyrosine397FAK in a time- and dose-dependent manner, which was correlated with the changes in trans-endothelial permeability. Our data indicated that dexmedetomidine is able to ameliorate remote pulmonary microvascular hyper-permeability induced by rI/R, at least in part, via FAK modulation.
Publication Date: 24-Jul-2016
Date of Acceptance: 10-Jul-2016
URI: http://hdl.handle.net/10044/1/39859
DOI: http://dx.doi.org/10.18632/oncotarget.10809
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 55990
End Page: 56001
Journal / Book Title: Oncotarget
Volume: 7
Issue: 35
Copyright Statement: This article is licensed under a Creative Commons Attribution 3.0 License.
Sponsor/Funder: British Journal of Anaesthesia
Royal College Of Anaesthetists
Funder's Grant Number: BJA / RCoA grants NIAA 2014
n/a
Keywords: FAK
Pathology Section
dexmedetomidine
endothelial Barrier
lung injury
α2-adrenoreceptor
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons