MicroRNA dysregulation in lung injury: the role of the miR-26a/EphA2 axis in regulation of endothelial permeability

American Journal of Physiology. Lung Cellular and Molecular Physiology
Ryan J GoodEva Nozik-Grayck

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression in many diseases, although the contribution of miRNAs to the pathophysiology of lung injury remains obscure. We hypothesized that dysregulation of miRNA expression drives the changes in key genes implicated in the development of lung injury. To test our hypothesis, we utilized a model of lung injury induced early after administration of intratracheal bleomycin (0.1 U). Wild-type mice were treated with bleomycin or PBS, and lungs were collected at 4 or 7 days. A profile of lung miRNA was determined by miRNA array and confirmed by quantitative PCR and flow cytometry. Lung miR-26a was significantly decreased 7 days after bleomycin injury, and, on the basis of enrichment of predicted gene targets, it was identified as a putative regulator of cell adhesion, including the gene targets EphA2, KDR, and ROCK1, important in altered barrier function. Lung EphA2 mRNA, and protein increased in the bleomycin-injured lung. We further explored the miR-26a/EphA2 axis in vitro using human lung microvascular endothelial cells (HMVEC-L). Cells were transfected with miR-26a mimic and inhibitor, and expression of gene targets and permeability was measured. miR-26a regulated expressi...Continue Reading

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Citations

Mar 13, 2020·Physiological Reports·Pavel Davizon-CastilloCassidy Delaney
Sep 29, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ayed AllawziEva Nozik-Grayck
Aug 13, 2020·International Journal of Molecular Sciences·Dianne VreekenJanine M van Gils
Jul 8, 2020·Pharmaceuticals·Sarah BaudetXavier Nicol
Dec 3, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Cassidy DelaneyEva S Nozik
Nov 13, 2020·Current Protein & Peptide Science·Carlos H I Ramos, Kehinde S Ayinde

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Methods Mentioned

BETA
bronchoalveolar
lavage
ELISA
PCR
transfection
protein assay
electrophoresis
confocal microscopy
Flow Cytometry
transfections

Software Mentioned

Image Laboratory
TargetScan
GraphPad
FluorChem HD 9900
Enrichr
Prism

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