Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients
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PROVIDER: PRJNA749028 | ENA |
REPOSITORIES: ENA
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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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| S-EPMC8584050 | biostudies-literature
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
Project description:To clarify the profile of in BALF exosome collected from mice infected with influenza virus, we infected 100000 pfu of A/Puerto Rico/8/1934 (PR8) strain. BALF was collected at 24, 48, and 72 hour post infection (hpi). For comparison of the profile of the miRNA in BALF exosome induced by innate immune response, we also intranasally inoculated mice with 50 μg of poly(I:C) and collected BALF at 72 hour post inoculation. We found that some miRNAs were common to both influenza virus infectiona and poly(I:C) inoculation, suggesting that exosomal miRNAs in BALF may function in the innate immune response to virus infection.
2018-06-08 | GSE107107 | GEO
Project description:Background: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the proliferative and fibrotic changes in the local environment in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular, comparative analysis of BALf cells from IPF and sarcoidosis patients. Methods: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real time PCR in 32 samples (11 IPF and 21 sarcoidosis). Results: The number of genes differentially expressed between IPF and sarcoidosis groups were 4832 (13359 probesets). Our cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis, transcription machinery. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. PCR verification showed higher expression of ANK3 in the sarcoidosis compared to the IPF group, and higher expression of MMP7 and PPBP in patients with IPF. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis. Conclusions: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells present in bronchoalveolar compartment and provided new data on the pathobiology of these ILDs. The changes of most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.
2019-05-02 | GSE121500 | GEO
Project description:Single Cell RNAseq of Whole Lung Dissociates from IPF, COPD and control lungs
2020-05-12 | GSE136831 | GEO
Project description:In the longtime challenge of identifying specific, easily-detectable and reliable biomarkers of interstitial lung diseases (ILDs), alternative biofluids, such as bronchoalveolar lavage fluid (BALF), have been extensively studied. In particular, BALF proteomics is gaining momentum and providing interesting new insights into the pathogenesis of ILDs, especially Idiopathic Pulmonary Fibrosis (IPF). Interest in the role of extracellular vesicles (EVs) in the pathogenesis of IPF has also grown. Though few, current studies on EVs in BALF of IPF patients focus mainly on miRNAs. To the best of our knowledge, the present study is therefore the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was chosen as EVs isolation technique and their purification was assessed by TEM, 2DE and LC-MS/MS. Our 2DE data and scatter plots showed considerable differences between the proteome of EVs and that of its supernatant and of whole BALF. Analysis of protein content and protein functions evidenced that EV proteins are predominantly involved in cytoskeleton remodeling, adenosine signaling, adrenergic signaling, C-peptide signaling and lipid metabolism. Our findings may suggest a wider system involvement in the disease pathogenesis and support the importance of pre-fractioning of complex samples, like BALF, in order to let low-abundant proteins-mediated pathways to emerge.
2021-08-06 | PXD025590 | Pride
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
2022-05-23 | GSE183973 | GEO
Project description:COPD is a heterogeneous condition without effective disease modifying therapies. Identification of novel inflammatory endotype markers such as extracellular vesicles (EVs), which are important intercellular messengers carrying microRNA (miRNA), may enable earlier diagnosis and disease stratification for a targeted treatment approach. Our aim was to identify differentially expressed EV miRNA in the lungs of COPD patients compared with healthy ex-smokers and determine whether they can help define inflammatory COPD endotypes. EV miRNA were isolated and sequenced from ex-smoking COPD patients and healthy ex-smoker bronchoalveolar lavage fluid. Results were validated with RT-qPCR and compared to differential inflammatory cell counts. Differential expression analysis identified five upregulated miRNA in COPD (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p and miR-625-3p) and three downregulated miRNA (miR-138-5p, miR-338-3p and miR-204-5p), all with a log2 fold change of >1/-1, FDR<0.05. These miRNAs correlated with disease defining characteristics such as FEF 25-75% (a small airways disease measure) and DLCO % (a surrogate measure of emphysema). Receiver operator curve analysis demonstrated miR-2110, miR-223-3p and miR-182-5p showed excellent combinatory predictive ability (AUC 0.91, p<0.0001) in differentiating between health and mild COPD. Furthermore, miR-223-3p and miR-338-3p correlated with airway eosinophilia and were able to distinguish “pure eosinophilic” COPD from other airway inflammatory subtypes (AUC 0.94 and 0.85 respectively). This is the first study to identify differentially expressed miRNA in COPD bronchoalveolar lavage fluid EVs. These findings suggest specific lung derived EV miRNA are a strong predictor of disease presence even in mild COPD. Furthermore, specific miRNA correlated with inflammatory cell numbers in COPD, and may have a role in defining inflammatory endotypes for future treatment stratification.
2022-12-05 | GSE218571 | GEO
Project description:Alveolar epithelial type II cells (AEC2) strictly regulate lipid metabolism to maintain surfactant synthesis. A loss in AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking related lung disease, chronic obstructive pulmonary disease (COPD). It is unclear if smoking alters lipid synthesis in AEC2 cells and if altering lipid metabolism in AEC2 cells contributes to COPD development. In this study, high throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN) in AEC2 cells (FasniAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, more severe air-space enlargement and were more susceptible to age-induced emphysema. FasniAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins and polyunsaturated fatty acid containing-phospholipids, as well as increased BALF surface tension. FasniAEC2 mice exposed to CS also had higher markers of ferroptosis in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.
2023-08-22 | GSE235644 | GEO