Transcriptomic and proteomic analyses reveal age-related extracellular matrix changes in the lung

Abstract

Background: Beyond its principal role as physical support, the lung extracellular matrix (ECM) is a bioactive scaffold involved in numerous biological processes including cellular growth, migration, survival, differentiation and metabolism. Detailed knowledge on the differences in composition of lung ECM with age is currently lacking. Therefore, the aim of this study was to investigate age‑related ECM differences in the lung.Methods: We used our previously identified age-related gene expression signature of the lung based on 1197 subjects (4-85 years) (Thorax, de Vries et al. 2018) and selected all ECM and ECM‑associated genes (matrisome core geneset). To determine whether age-related transcriptomic differences were also present at the protein level, we compared the significant age-related ECM genes (FDR <0.05) with the significant age-related proteins from lung tissue proteomics dataset from 9 subjects (49-76 years) (FDR<0.05). Immunohistochemistry was used to localize the age-related ECM proteins in the lung.Results: Analyses of transcriptomic and proteomic data identified 9 ECM proteins that were increased with aging at both the gene and protein level, including Type I alpha 1 collagen (COL1A1), COL6A1, COL6A2, COL14A1, fibulin-2 (FBLN2), latent transforming growth factor beta binding protein 4 (LTBP4), lumican (LUM), and osteoglycin (OGN). All proteins were detected in lung tissue and localized to the airway, parenchyma and blood vessels. The increased deposition of these proteins upon aging might contribute to remodeling of the ECM in the airways and parenchyma. Thus, these differences in lung ECM composition with age may impact biological processes and therefore contribute to the development of chronic lung diseases, such as COPD in the elderly.FootnotesCite this article as: ERJ Open Research 2020; 6: Suppl. 5, 57.This is an ERS Lung Science Conference 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).