Airway Smooth Muscle Inflammation Is Regulated by MicroRNA-145 in COPD.

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

Retraction Note: The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide (Respiratory Research, (2018), 19, 1, (85), 10.1186/s12931-018-0788-x)

The Editors-in-Chief have retracted this article. After publication concerns were raised about two of the figures, specifically: • In Figure 3a, the MPST blot for non-smokers appears to be the same as the CBS blot for smokers. • In Figure 5a, the beta-actin blot for smokers appears to be the same as the beta-actin blot for smokers in Figure 3c in a previous article [1]. An investigation by Imperial College into the integrity of these images was unable to reach a conclusion as it was established that the raw data and images from this study are not available for examination; it was therefore recommended that the article be retracted. Bernadett Tildy, Alberto Papi, Paolo Casolari, Gaetano Caramori, Karen Limbert Rempel, Andrew J. Halayko, Ian Adcock and Kian Fan Chung agree with this retraction. Mark Perry has not responded to correspondence from the Publisher about this retraction

Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT

The solid concentration of pulmonary mucus (wt%) is critical to respiratory health. In patients with respiratory disease, such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disorder (COPD), mucus hydration is impaired, resulting in high wt%. Mucus with high wt% is a hallmark of pulmonary disease that leads to obstructed airways, inflammation, and infection. Methods to measure mucus hydration in situ and in real-time are needed for drug development and personalized therapy. We employed plasmonic gold nanorod (GNR) biosensors that intermittently collide with macromolecules comprising the mucus mesh as they self-diffuse, such that GNR translational diffusion (DT) is sensitive to wt%. GNRs are attractive candidates for bioprobes due to their anisotropic optical scattering that makes them easily distinguishable from native tissue using polarization-sensitive OCT. Using principles of heterodyne dynamic light scattering, we developed diffusion-sensitive optical coherence tomography (DS-OCT) to spatially-resolve changing DT in real-time. DS-OCT enables, for the first time, direct monitoring of changes in nanoparticle diffusion rates that are sensitive to nanoporosity with spatial and temporal resolutions of 4.7 μm and 0.2 s. DS-OCT therefore enables us to measure spatially-resolved changes in mucus wt% over time. In this study, we demonstrate the applicability of DS-OCT on well-differentiated primary human bronchial epithelial cells during a clinical mucus-hydrating therapy, hypertonic saline treatment (HST), to reveal, for the first time, mucus mixing, cellular secretions, and mucus hydration on the micrometer scale that translate to long-term therapeutic effects