Transcriptomic and network analysis identifies shared and unique pathways and immune changes across fibrotic
Wenhao Liu1, Kangping Huang1, Xin-Zhuang Yang2
1Eight-Year Program of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Aging
|February 13, 2024
Summary
This study reveals common and distinct molecular pathways in three fibrotic lung diseases: idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease-associated ILD (CTD-ILD). Findings offer insights into pathogenesis and potential therapeutic targets for these progressive lung conditions.
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Interstitial lung disease (ILD) comprises various chronic inflammatory and fibrotic lung disorders.
- Idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease-associated ILD (CTD-ILD) share fibrosis but differ in causes.
- Understanding distinct mechanisms in these ILDs is crucial for targeted therapies.
Purpose of the Study:
- To identify shared and specific molecular and cellular pathways in IPF, fHP, and CTD-ILD.
- To explore the underlying mechanisms of progressive fibrosis in these distinct ILD subtypes.
- To provide a foundation for developing novel therapeutic strategies.
Main Methods:
- Transcriptome data from fibrotic lung tissues of IPF, fHP, and CTD-ILD patients were analyzed.
- Functional annotation, network, and pathway analyses were performed.
- The xCell deconvolution algorithm predicted immune cell infiltration.
Main Results:
- A common fibrosis module linked to extracellular matrix (ECM) dynamics and p53 transcription factors was identified.
- IPF showed specific neuron-related processes; fHP highlighted B cell signaling and IgA production.
- CTD-ILD exhibited enriched chemokine processes and predicted infiltration of active dendritic cells (aDCs).
Conclusions:
- Shared and distinct molecular and cellular pathways were elucidated across IPF, fHP, and CTD-ILD.
- These findings enhance understanding of the pathogenesis of these fibrotic lung diseases.
- The study identifies potential targets for future therapeutic interventions.
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