MicroRNA modulate alveolar epithelial response to cyclic stretch
<p>Abstract</p> <p>Background</p> <p>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 fo...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-04-01
|
| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/13/154 |
| _version_ | 1811298801947770880 |
|---|---|
| author | Yehya Nadir Yerrapureddy Adi Tobias John Margulies Susan S |
| author_facet | Yehya Nadir Yerrapureddy Adi Tobias John Margulies Susan S |
| author_sort | Yehya Nadir |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-04-13T06:24:50Z |
| format | Article |
| id | doaj.art-8bc005606ba04b92a52fbc2ea2c765d8 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-13T06:24:50Z |
| publishDate | 2012-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-8bc005606ba04b92a52fbc2ea2c765d82022-12-22T02:58:28ZengBMCBMC Genomics1471-21642012-04-0113115410.1186/1471-2164-13-154MicroRNA modulate alveolar epithelial response to cyclic stretchYehya NadirYerrapureddy AdiTobias JohnMargulies Susan S<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/13/154 |
| spellingShingle | Yehya Nadir Yerrapureddy Adi Tobias John Margulies Susan S MicroRNA modulate alveolar epithelial response to cyclic stretch BMC Genomics |
| title | MicroRNA modulate alveolar epithelial response to cyclic stretch |
| title_full | MicroRNA modulate alveolar epithelial response to cyclic stretch |
| title_fullStr | MicroRNA modulate alveolar epithelial response to cyclic stretch |
| title_full_unstemmed | MicroRNA modulate alveolar epithelial response to cyclic stretch |
| title_short | MicroRNA modulate alveolar epithelial response to cyclic stretch |
| title_sort | microrna modulate alveolar epithelial response to cyclic stretch |
| url | http://www.biomedcentral.com/1471-2164/13/154 |
| work_keys_str_mv | AT yehyanadir micrornamodulatealveolarepithelialresponsetocyclicstretch AT yerrapureddyadi micrornamodulatealveolarepithelialresponsetocyclicstretch AT tobiasjohn micrornamodulatealveolarepithelialresponsetocyclicstretch AT marguliessusans micrornamodulatealveolarepithelialresponsetocyclicstretch |