O'Leary, L;
Sevinç, K;
Papazoglou, IM;
Tildy, B;
Detillieux, K;
Halayko, AJ;
Chung, KF;
(2016)
Airway Smooth Muscle Inflammation Is Regulated by MicroRNA-145 in COPD.
FEBS Letters
, 590
(9)
pp. 1324-1334.
10.1002/1873-3468.12168.
Preview |
Text
Perry_miR-145 COPD.pdf Download (611kB) | Preview |
Abstract
Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)-β. MicroRNAs are short, non-coding gene transcripts involved in the negative regulation of specific target genes, through their interactions with messenger RNAs. Previous studies have proposed that microRNA-145 (miR-145) may interact with SMAD3, an important downstream signalling molecule of the TGF-β pathway. TGF-β was used to stimulate primary human ASM cells isolated from healthy non-smokers, healthy smokers and COPD patients. This resulted in a TGF-β-dependent increase in CXCL8 and IL-6 release, most notably in the cells from COPD patients. TGF-β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR-145 expression. Regulation of miR-145 was found to be negatively controlled by pathways involving the MAP kinases, MEK-1/2 and p38 MAPK. Subsequent, overexpression of miR-145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL-6 and CXCL8 release, to levels comparable to the non-smoker controls. Therefore, this study suggests that miR-145 negatively regulates pro-inflammatory cytokine release from ASM cells in COPD by targeting SMAD3.
| Type: | Article |
|---|---|
| Title: | Airway Smooth Muscle Inflammation Is Regulated by MicroRNA-145 in COPD |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/1873-3468.12168 |
| Publisher version: | http://dx.doi.org/10.1002/1873-3468.12168 |
| Language: | English |
| Additional information: | Copyright © 2016 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1485190 |
Archive Staff Only
 |
View Item |
