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Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age‑associated differences in lung ECM is currently limited. In this study we aimed to identify and localize age‑associated ECM differences in human lung using comprehensive transcriptomic, proteomic and immunohistochemical analyses. Our previously identified age-associated gene expression signature of the lung was re‑analyzed limiting it to an aging signature based on 270 control patients (37-80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age‑associated transcriptomic differences on protein level, we compared the age-associated ECM genes (FDR <0.05) with a profile of age‑associated proteins identified from a lung tissue proteomics dataset from 9 control patients (49-76 years) (FDR<0.05). Extensive immunohistochemical analysis was used to localize and semi-quantify the age-associated ECM differences in lung tissues from 62 control patients (18-82 years). Comparative analysis of transcriptomic and proteomic data identified 7 ECM proteins with higher expression with age at both gene and protein level: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4 and LUM. With immunohistochemistry we demonstrated higher protein level with age for COL6A2 in whole tissue, parenchyma, airway wall and blood vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in lung parenchyma. Our study revealed that higher age is associated with lung ECM remodeling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility for developing chronic lung diseases.
AJP Lung Cellular and Molecular Physiology – The American Physiological Society
Published: Jun 1, 2023
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