Journal article
Post-Transcriptional Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Expression and Function by MicroRNAs
American journal of respiratory cell and molecular biology, Vol.49(4), pp.544-551
10/2013
DOI: 10.1165/rcmb.2012-0430OC
PMCID: PMC3824042
PMID: 23646886
Abstract
MicroRNAs (miRNAs) are increasingly recognized as important posttranscriptional regulators of gene expression, and changes in their actions can contribute to disease states. Little is understood regarding miRNA functions in the airway epithelium under normal or diseased conditions. We profiled miRNA expression in well-differentiated primary cultures of human cystic fibrosis (CF) and non-CF airway epithelia, and discovered that miR-509–3p and miR-494 concentrations were increased in CF epithelia. Human non-CF airway epithelia, transfected with the mimics of miR-509–3p or miR-494, showed decreased cystic fibrosis transmembrane conductance regulator (CFTR) expression, whereas their respective anti-miRs exerted the opposite effect. Interestingly, the two miRNAs acted cooperatively in regulating CFTR expression. Upon infecting non-CF airway epithelial cells with
Staphylococcus aureus
, or upon stimulating them with the proinflammatory cytokines TNF-α or IL-1β, we observed an increased expression of both miRNAs and a concurrent decrease in CFTR expression and function, suggesting that inflammatory mediators may regulate these miRNAs. Transfecting epithelia with anti-miRs for miR-509–3p and miR-494, or inhibiting NF-κB signaling before stimulating cells with TNFα or IL-1β, suppressed these responses, suggesting that the expression of both miRNAs was responsive to NF-κB signaling. Thus, miR-509–3p and miR-494 are dynamic regulators of CFTR abundance and function in normal, non-CF airway epithelia.
Details
- Title: Subtitle
- Post-Transcriptional Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Expression and Function by MicroRNAs
- Creators
- Shyam Ramachandran - Department of PediatricsPhilip H Karp - Department of Internal MedicineSamantha R Osterhaus - Department of PediatricsPeng Jiang - Department of Internal MedicineChristine Wohlford-Lenane - Department of PediatricsKim A Lennox - Integrated DNA Technologies, Coralville, IowaAshley M Jacobi - Integrated DNA Technologies, Coralville, IowaKal Praekh - Department of Cardiothoracic SurgeryScott D Rose - Integrated DNA Technologies, Coralville, IowaMark A Behlke - Integrated DNA Technologies, Coralville, IowaYi Xing - Department of Internal MedicineMichael J Welsh - Department of Internal MedicinePaul B McCray - Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.49(4), pp.544-551
- DOI
- 10.1165/rcmb.2012-0430OC
- PMID
- 23646886
- PMCID
- PMC3824042
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 10/2013
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020788402771
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