Central lung gene expression associates with myofibroblast features in idiopathic pulmonary fibrosis.

Autor:	Huang Y; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Guzy R; Section of Pulmonary & Critical Care Medicine, University of Chicago, Chicago, Illinois, USA., Ma SF; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Bonham CA; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Jou J; Department of Surgery, University of Illinois, Peoria, Illinois, USA., Schulte JJ; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA., Kim JS; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Barros AJ; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Espindola MS; Division of Pulmonary & Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Husain AN; Department of Pathology, University of Chicago, Chicago, Illinois, USA., Hogaboam CM; Division of Pulmonary & Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Sperling AI; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA., Noth I; Division of Pulmonary & Critical Care Medicine, University of Virginia, Charlottesville, Virginia, USA IN2C@hscmail.mcc.virginia.edu.
Jazyk:	angličtina
Zdroj:	BMJ open respiratory research [BMJ Open Respir Res] 2023 Feb; Vol. 10 (1).
DOI:	10.1136/bmjresp-2022-001391
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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