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- Strickson, Sam, et al.
(författare)
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Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex
- 2023
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Ingår i: European Respiratory Journal. - 0903-1936. ; 62:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. Methods In vitro epithelial damage assays and three-dimensional, air–liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. Results We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. Conclusions Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and mucoobstructive features in COPD.
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| 2. |
- Horgan, Briony, et al.
(författare)
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Mineralogy, Morphology, and Emplacement History of the Maaz Formation on the Jezero Crater Floor From Orbital and Rover Observations
- 2023
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 128:8
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Tidskriftsartikel (refereegranskat)abstract
- The first samples collected by the Perseverance rover on the Mars 2020 mission were from the Maaz formation, a lava plain that covers most of the floor of Jezero crater. Laboratory analysis of these samples back on Earth would provide important constraints on the petrologic history, aqueous processes, and timing of key events in Jezero crater. However, interpreting these samples requires a detailed understanding of the emplacement and modification history of the Maaz formation. Here we synthesize rover and orbital remote sensing data to link outcrop-scale interpretations to the broader history of the crater, including Mastcam-Z mosaics and multispectral images, SuperCam chemistry and reflectance point spectra, Radar Imager for Mars' subsurface eXperiment ground penetrating radar, and orbital hyperspectral reflectance and high-resolution images. We show that the Maaz formation is composed of a series of distinct members corresponding to basaltic to basaltic-andesite lava flows. The members exhibit variable spectral signatures dominated by high-Ca pyroxene, Fe-bearing feldspar, and hematite, which can be tied directly to igneous grains and altered matrix in abrasion patches. Spectral variations correlate with morphological variations, from recessive layers that produce a regolith lag in lower Maaz, to weathered polygonally fractured paleosurfaces and crater-retaining massive blocky hummocks in upper Maaz. The Maaz members were likely separated by one or more extended periods of time, and were subjected to variable erosion, burial, exhumation, weathering, and tectonic modification. The two unique samples from the Maaz formation are representative of this diversity, and together will provide an important geochronological framework for the history of Jezero crater.
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