Abstract
Background: COPD involves emphysema and small airway wall thickening. Chronic inflammation and aberrant repair processes play a role in both, but the exact mechanisms are unknown. Pulmonary fibroblasts are key regulators of repair and may be affected by chronic inflammation. So far, a comprehensive analysis comparing COPD and control fibroblasts is lacking, especially on protein level.
Aim: To identify COPD-related protein changes in lung fibroblasts using a shotgun proteomics approach.
Methods: Lung fibroblasts were harvested from 13 stage IV COPD patients and 10 matched controls. Isolated proteins were subjected to shotgun proteomic analysis with LC-MS/MS. Linear regression modeling compared COPD patients with controls, corrected for age and sex. Differentially expressed proteins were compared to RNA sequencing data from the same cohort, and cross-referenced with literature via high-throughput text-mining with TenWise KMAP-API.
Results: After removing lowly expressed proteins, we identified 774 proteins of which 40 proteins were significantly differentially expressed between COPD and control fibroblasts (FDR < 0.05). The most significant being HNRNPA2B1 and FHL1, and TUBA1C and HNRNPA1 having the highest fold change. TUBA1C was also significant at the transcript level. Cross-referencing with literature revealed that 13 proteins were previously associated with COPD, including FHL1 and GSTP-1 with 5 and 42 hits respectively.
Conclusions: We identified 40 differentially expressed proteins in COPD compared to control fibroblasts, including previously described COPD proteins FHL1 and GSTP1, as well as 27 new proteins, providing several intriguing new research targets for further functional studies in COPD.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA1215.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021