Spatially Resolved Metabolomics Reveals Metabolic Heterogeneity Among Pulmonary Fibrosis

Area of Science:

• Pulmonary medicine
• Metabolomics
• Pathology

Background:

• Pulmonary fibrosis (PF) is a severe, progressive lung disease with complex mechanisms and tissue heterogeneity.
• Understanding the spatial organization of metabolites in lung tissues is crucial for studying PF.
• Idiopathic pulmonary fibrosis (IPF) and silicosis represent distinct forms of lung fibrosis with different pathological characteristics.

Purpose of the Study:

• To investigate and compare the metabolic heterogeneity between idiopathic pulmonary fibrosis (IPF) and silicosis.
• To identify specific metabolic pathways and metabolites that differ spatially between these two fibrotic lung diseases.
• To explore potential metabolic targets for therapeutic intervention in pulmonary fibrosis.

Main Methods:

• Utilized advanced spatially-resolved metabolomics techniques, including high-resolution mass spectrometry imaging.
• Analyzed lung tissue sections from mouse models of IPF and silicosis.
• Performed histological analysis to confirm fibrosis and characterize pathological features.
• Quantified and mapped over 260 metabolites to identify spatial metabolic differences.

Main Results:

• Confirmed distinct histological features for IPF (alveolar destruction, collagen deposition) and silicosis (nodule formation).
• Revealed significant differences in phospholipid metabolism, purine/pyrimidine metabolism, and the TCA cycle between IPF and silicosis.
• Observed elevated phosphocholine in silicosis, reduced phosphocholine in IPF, and decreased carnitine in both.
• Found increased glycolytic activity in both models, with opposing trends in TCA cycle intermediates.

Conclusions:

• Pulmonary fibrosis exhibits significant spatial metabolic heterogeneity between IPF and silicosis.
• Specific metabolic pathways and metabolites show distinct alterations in each fibrosis type.
• These findings suggest potential novel metabolic targets for developing therapeutic strategies against pulmonary fibrosis.