Central lung gene expression associates with myofibroblast features in idiopathic pulmonary fibrosis
Year: 2023
Type: article
Study design: Observational Study
Abstract: Rationale Contribution of central lung tissues to pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unknown. Objective To ascertain the relationship between cell types of IPF-central and IPF-peripheral lung explants using RNA sequencing (RNA-seq) transcriptome. Methods Biopsies of paired IPF-central and IPF-peripheral along with non-IPF lungs were selected by reviewing H&E data. Criteria for differentially expressed genes (DEG) were set at false discovery rate <5% and fold change >2. Computational cell composition deconvolution was performed. Signature scores were computed for each cell type. Findings Comparison of central IPF versus non-IPF identified 1723 DEG (1522 upregulated and 201 downregulated). Sixty-two per cent (938/1522) of the mutually upregulated genes in central IPF genes were also upregulated in peripheral IPF versus non-IPF. Moreover, 85 IPF central-associated genes (CAG) were upregulated in central IPF versus both peripheral IPF and central non-IPF. IPF single-cell RNA-seq analysis revealed the highest CAG signature score in myofibroblasts and significantly correlated with a previously published activated fibroblasts signature (r=0.88, p=1.6×10 −4 ). CAG signature scores were significantly higher in IPF than in non-IPF myofibroblasts (p=0.013). Network analysis of central-IPF genes identified a module significantly correlated with the deconvoluted proportion of myofibroblasts in central IPF and anti-correlated with inflammation foci trait in peripheral IPF. The module genes were over-represented in idiopathic pulmonary fibrosis signalling pathways. Interpretation Gene expression in central IPF lung regions demonstrates active myofibroblast features that contributes to disease progression. Further elucidation of pathological transcriptomic state of cells in the central regions of the IPF lung that are relatively spared from morphological rearrangements may provide insights into molecular changes in the IPF progression.
Source: BMJ Open Respiratory Research
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,085
Awards: Architectural structure and regulation of TOLLIP in IPF, T cells in idiopathic pulmonary fibrosis, Epithelial-Mesenchymal Interactions in Pulmonary Fibrosis and Chronic Allograft Dysfunction (CLAD), IRF4+ respiratory dendritic cells in type 2 inflammatory responses, Mechanism of Fibroblast Growth Factor 2-Mediated Alveolar Epithelial Repair, G4498383146, 1/2 Prospective tReatment EffiCacy in IPF uSlng genOtype for Nac Selection (PRECISIONS) trial and Molecular Endophenotyping in Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases study, Role of polyunsaturated fatty acids in pulmonary fibrosis
OpenAlex ID: W4318815856