Cytosolic Calreticulin Inhibits Microwave Radiation‐Induced Microvascular Endothelial Cell Injury Through the Integrin‐Focal Adhesion Kinase Pathway. (November 2014)

• Record Type: Journal Article
• Authors: Xu, Fei‐Fei; Tao, Tian‐Qi; Wang, Xiao‐Reng; Li, Yu‐Zhen; Song, Dan‐Dan; Liu, Mi; Liu, Xiu‐Hua
• Is Part Of: Microcirculation. Volume 21:Number 8(2014:Nov.)
• Page Start: 717
• Page End: 729
• Publication Date: 2014-11
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12153
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12153-abs-0001"> <title>Abstract</title> <sec id="micc12153-sec-0001" sec-type="section"> <title>Objective</title> <p>To determine the effects of cytosolic CRT on MR‐induced MMEC injury, and the underlying mechanism.</p> </sec> <sec id="micc12153-sec-0002" sec-type="section"> <title>Methods</title> <p>MMECs were randomized into eight groups: control, AdCRT (infected with pAdCMV/V5‐DEST‐CRT adenovirus), stCRT (transfected with rCRT‐siRNAs), Mock (transfected with scrambled siRNAs), MR (exposed to MR for six minutes), AdCRT + MR, stCRT + MR, and Mock + MR. The magnitude of cell injury were assessed by Annexin V‐PI staining, LDH activity in culture medium, MMEC migration ability, ultrastructure and cytoskeletal stability. Subcellular colocalization of CRT and ConA or integrin were evaluated by immunocytochemistry. The mRNA and protein expression levels of target genes were examined by qRT‐PCR and western blotting, respectively.</p> </sec> <sec id="micc12153-sec-0003" sec-type="section"> <title>Results</title> <p>MR‐induced cytotoxicity was dose‐dependent. Overexpression of cytosolic CRT suppressed MR injury, shown as decreased cell apoptosis, reduced LDH activity, enhanced cell migration capability, and maintenance of ultrastructure and cytoskeleton integrity. Conversely, CRT deficiency aggravated MR‐induced injury. Exposure of AdCRT MMECs to MR promoted membrane translocation of CRT and the interaction of CRT‐integrin‐<italic>α</italic>. Correlation analysis revealed that integrin‐<italic>α</italic> expression or FAK phosphorylation was positively associated with cytosolic CRT expression.</p> </sec> <sec id="micc12153-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Cytosolic CRT inhibits MR‐induced MMEC injury through activation of the integrin‐FAK pathway.</p> </sec> </abstract>