Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis
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ABSTRACT:
PROVIDER: PRJNA763978 | ENA |
REPOSITORIES: ENA
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Project description:Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: We aimed to identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microCT measures, fHP cores were clustered into a mild, moderate and severe fibrosis group. Gene expression profiles were assessed using Weighted Gene Co-expression Network Analysis (WGCNA), xCell, gene ontology and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with IPF. The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, bronchoalveolar lavage samples and computed tomography scans. Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B-cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behaviour in a separate clinical fHP cohort. Conclusion: We identified six molecular traits which characterise the morphological progression of fHP and associate with in vivo clinical behaviour. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent, rather than by diagnosis alone.
2022-01-01 | GSE184316 | GEO
Project description:Transcriptional analysis of non-fibrotic NAFLD progression
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Project description:Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of CHP subjects have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). However, the molecular relationship between CHP and IPF is not well understood. We report an RNA-seq based transcriptomic analysis for whole lung tissues from CHP, IPF and control subjects.
2020-07-01 | GSE150910 | GEO
Project description:To further understand the pathologic microenvironment in IPF, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish normal and IPF lung in normal-looking, fibrotic foci and hyperplastic areas of IPF lung. Four IPF lungs were dissected into normal-looking, fibrotic foci and hyperplastic areas by Laser-Capture-Microdissection. Gene expression analysis showed that 638 significantly different genes were identified that clearly distinguished the different IPF microenvironments . Among them, MMP19 was revealed as one of the most significantly up-regulated genes that distinguished normal looking epithelial cells (N) to hyperplastic epithelial cells, MMP19 up-regulation in IPF lungs was verified by immunohistochemical (IHC), qRT-PCR and Western-blot. IPF lungs are heterogeneity complex, which comprise normal looking area, fibrotic foci and hyperplastic area. In this study we separated the normal, fibrotic foci and hyperplastic area by LCM and employed Agilent whole genome gene expression microarray profiling to identify genes with the potential to distinguish the unique microenironment of IPF
2013-01-11 | E-GEOD-35309 | biostudies-arrayexpress
Project description:Causes hypersensitivity pneumonitis
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Project description:IL-2 inducible tyrosine kinase (Itk) is a Tec family non-receptor tyrosine kinase that is known to regulate T-helper cell differentiation and function. It has been established that Itk postively regulates T helper 17 cells. However, in a model of hypersensitivity pneumonitis we found T helper 17 cells develop independently of Itk. Therefore, we compared the transcriptomes of WT and Itk-/- T helper 17 cells following exposure with Saccharopolyspora rectivirgula by RNA sequencing.
2024-01-28 | GSE165711 | GEO
Project description:Approximately 60-70% of patients with pulmonary sarcoidosis have a good outcome, with disease that resolves spontaneously. It is unclear why some patients progress to fibrotic disease, and there is currently no marker that differentiates these patients from those with self-limiting lung disease. Using the Affymetrix Human Gene 1.0 ST Array, we examined gene expression in lung tissue samples obtained using bronchoscopic transbronchial biopsy from 8 patients with active but self-limiting pulmonary sarcoidosis and 7 with active, progressive, fibrotic pulmonary disease. Analyses were performed to identify differentially expressed genes between the two groups, and to test for enrichment of sets of genes associated with defined biological processes from the Gene Ontology Consortium, as well as with gene sets derived from published data for idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP).
2010-01-31 | GSE19976 | GEO
Project description:Background & Aims: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this study is to define transcriptional changes in early, non-fibrotic NAFLD using a biopsy-proven non-fibrotic NAFLD cohort. Methods: We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 with NAS ≤3, 17 with NAS ≥5) and 21 healthy controls and compared changes in expression of 594 genes involved in innate immune function. Results: Compared to healthy controls, NAFLD patients with NAS ≥5 had differential expression of 211 genes, while those with NAS ≤3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS ≤3, 8.28-fold in NAS ≥5) and CXCL10 (2.27-fold in NAS ≤3, 8.28-fold in NAS ≥5) gene expression were significantly upregulated with histologic progression of NAFLD.
2020-07-08 | GSE151158 | GEO
Project description:RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung
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