Abstract
Rationale
In COPD there is an increase in airway smooth muscle (ASM) mass. ASM cells may contribute to airway inflammation and remodelling through the secretion of inflammatory cytokines and increased proliferation. We have previously demonstrated that ASM cells in COPD are of a hyperproliferative state and release greater amounts of IL-6 & CXCL8. microRNAs (miRNAs) have recently emerged as important regulatory molecules in COPD, and we have previously demonstrated the role of these in controlling ASM cell proliferation in asthma. We hypothesis that miRNAs are important in controlling the aberrant phenotype observed in ASM cells from patients with COPD.
Methods
Human primary ASM cells were grown from individuals classified as being healthy, smokers, or those with COPD (n = 9). Cells were stimulated with TGF-β, and the expression of miRNA & mRNA levels were measured by RT-PCR. Computational prediction algorithms were used to identify targets of miR-145, and said miRNA was knocked-down and over-expressed using mimics and inhibitors, respectively.
Results
miR-145 was significantly up-regulated in ASM cells from patients with COPD compared against healthy subjects and smokers. Conversely, SMAD3 (a key mRNA of the TGF-β signalling pathway), was significantly decreased in the same samples.
Inhibiting miR-145 in ASM cells from COPD patients reduced the increased IL-6 & CXCL8 release and returned the levels of SMAD3 back to levels comparable to that of healthy individuals.
Conclusions
This is the first time that miR-145 has been demonstrated to be fundamental in controlling the increased inflammatory state of ASM cells from COPD patients. This miRNA may not only act as a novel biomarker for COPD, but may also be a novel target for treatment.
- © 2014 ERS