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06:03
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
746
Dysregulated Cell-Cell Communication Characterizes Pulmonary Fibrosis
Jonathan S Kurche1,2, Ian T Stancil3, Jacob E Michalski4
1Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cells
|October 27, 2022
Summary
The MUC5B genetic variant, a key risk factor for idiopathic pulmonary fibrosis (IPF), influences lung fibrosis by altering alveolar epithelial cells. This study reveals mechanisms involving ADAM17 and IL6 signaling in IPF pathogenesis.
Area of Science:
- Pulmonary Medicine
- Genetics
- Molecular Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing fibrotic replacement of gas exchange units.
- A specific genetic variant in the MUC5B mucin promoter is the strongest known risk factor for IPF.
Purpose of the Study:
- To investigate how the MUC5B genetic variant influences IPF development.
- To identify molecular mechanisms by which the MUC5B variant impacts lung epithelia in fibrotic environments.
Main Methods:
- Utilized the NicheNet R package and single-cell RNA sequencing data.
- Analyzed transcriptomes of alveolar epithelial cells from control, MUC5B variant, and fibrotic lung environments.
- Validated findings using single nuclear RNA sequencing and immunofluorescence.
Main Results:
- Loss of type-I alveolar epithelial cells (AECI) was observed in fibrotic lung transcriptomes.
- AECI transcriptomes showed enrichment of IL6 and AREG signatures.
- The protease ADAM17, upstream of IL6 trans-signaling, was enriched in MUC5B variant donors and validated by immunofluorescence.
Conclusions:
- The MUC5B variant is implicated in IPF pathogenesis through mechanisms involving AECI loss and altered signaling pathways.
- Enhanced ADAM17 expression in MUC5B variants suggests a role in IPF maintenance and progression.
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