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The soluble factor milieu in IPF and in COPD exacerbations dysregulates epithelial differentiation

ABSTRACT: The soluble factor milieu in IPF and in COPD exacerbations dysregulates epithelial differentiation

PROVIDER: PRJNA1027466 | ENA |

REPOSITORIES: ENA

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The soluble factor milieu in IPF and in COPD exacerbations dysregulates epithelial differentiation

Project description:In idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), epithelial abnormalities are present including bronchiolization and alveolar cell death and dysfunction. As epithelial progenitor cells are directed by their microenvironment, we hypothesized that changes in the microenvironment disrupt normal epithelial growth and differentiation. We therefore mimicked the soluble factor microenvironment in IPF using an IPF cocktail (IPFc), composed of 9 factors which are increased in IPF lungs (CCL2, IL-1β, IL-4, IL-8, IL-13, IL-33, TGF-β, TNFα and TSLP) and in COPD exacerbations using an exacerbation cocktail (EC) composed of 4 factors that are increased during an exacerbation of COPD (TNFα, IL-1β, IL-6, IL-8). We asked whether the soluble factor milieu in IPF and COPD exacerbations affects epithelial growth and differentiation. Mouse lung organoids (primary EpCAM+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial growth and differentiation. Organoids exposed to IPFc, EC or TGF-β (as a comparator) were resorted into EpCAM+ and CCL206 fractions, and subjected to RNA-sequencing.

2024-04-30 | GSE245259 | GEO

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Project description:Viruses in acute exacerbations of idiopathic pulmonary fibrosis Keywords: viral detection BAL from patients with acute exacerbations of IPF and stable IPF were hybridized to a pan-viral cDNA microarray to evaluate the presence of virus during these episodes

2011-03-03 | E-GEOD-27578 | biostudies-arrayexpress

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2014-06-01 | E-GEOD-54837 | biostudies-arrayexpress

Altered gene expression in blood and sputum from COPD patients with frequent exacerbations

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Transcriptome analysis to investigate COPD exacerbations to influenza infection

Project description:Lung infection by influenza A viruses is a common cause of disease exacerbations in patients with chronic obstructive pulmonary disease (COPD), however, this process is difficult to study in human patients. Here we used a microfluidic human lung airway-on-a-chip (Airway Chip) lined by primary human bronchial epithelium interfaced with primary human pulmonary microvascular endothelium to model this process in vitro. Airway Chips containing bronchial epithelial cells from COPD patients successfully replicated the increased sensitivity to the lung airway to infection by both influenza H1N1 and H3N2 viruses compared to chips lined by epithelium from healthy donors, including enhanced viral loads and increased production of inflammatory cytokines. Transcriptomics analysis of the healthy and COPD epithelium following infection with influenza H1N1 virus on-chip resulted in identification of several novel markers of COPD

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Transcriptome analysis to investigate COPD exacerbations to influenza infection

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Noncoding SNPs decrease expression of FABP5 during COPD exacerbations

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Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

Project description:Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Considering this, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, we found three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.

2021-08-13 | GSE180651 | GEO

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