title: MicroRNA modulate alveolar epithelial response to cyclic stretch.
abstract: BACKGROUND
  MicroRNAs (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).
  
  
  RESULTS
  RAECs 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104-6321, USA.
authors.forename: Nadir
authors.initials: N
authors.lastname: Yehya
authors.forename: Adi
authors.initials: A
authors.lastname: Yerrapureddy
authors.forename: John
authors.initials: J
authors.lastname: Tobias
authors.forename: Susan S
authors.initials: SS
authors.lastname: Margulies
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D002463:Cell Membrane Permeability / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012984:Software; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs