MicroRNA modulate alveolar epithelial response to cyclic stretch

BMC Genomics

Research Article

John Tobias¹  Susan S Margulies²  Adi Yerrapureddy²  Nadir Yehya³ 

[1] Bioinformatics Core, University of Pennsylvania, 19104, Philadelphia, PA, USA;Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, 19104-6321, Philadelphia, PA, USA;Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, 19104-6321, Philadelphia, PA, USA;Division of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, 19104, Philadelphia, PA, USA;

关键词: miRNA Expression;    Alveolar Epithelial Cell;    Locked Nucleic Acid;    Cyclic Stretch;    Epithelial Permeability;   

DOI  :  10.1186/1471-2164-13-154

 received in 2011-05-07, accepted in 2012-04-26,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are post-transcriptional regulators of gene expression implicated in multiple cellular processes. Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator-induced lung injury. We propose that miRNAs may regulate some of the stretch response, and therefore hypothesized that miRNAs would be differentially expressed between cyclically stretched and unstretched rat alveolar epithelial cells (RAECs).ResultsRAECs were isolated and cultured to express type I epithelial characteristics. They were then equibiaxially stretched to 25% change in surface area at 15 cycles/minute for 1 hour or 6 hours, or served as unstretched controls, and miRNAs were extracted. Expression profiling of the miRNAs with at least 1.5-fold change over controls revealed 42 miRNAs were regulated (34 up and 8 down) with stretch. We validated 6 of the miRNAs using real-time PCR. Using a parallel mRNA array under identical conditions and publicly available databases, target genes for these 42 differentially regulated miRNAs were identified. Many of these genes had significant up- or down-regulation under the same stretch conditions. There were 362 down-regulated genes associated with up-regulated miRNAs, and 101 up-regulated genes associated with down-regulated miRNAs. Specific inhibition of two selected miRNAs demonstrated a reduction of the increased epithelial permeability seen with cyclic stretch.ConclusionsWe conclude that miRNA expression is differentially expressed between cyclically stretched and unstretched alveolar epithelial cells, and may offer opportunities for therapeutic intervention to ameliorate stretch-associated alveolar epithelial cell dysfunction.

【 授权许可】

Unknown   
© Yehya et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.