COPD-associated changes in lung extracellular matrix

Abstract

<b>Introduction:</b> The pathology of COPD displays characteristics of accelerated aging in the lungs. One such feature is abnormal extracellular matrix (ECM) turnover, particularly in the small airway walls. Previously, age was shown to be associated with higher expression of several ECM proteins i.e. collagen type I alpha 1 (COL1A1), COL6A1, COL6A2, COL14A1, lumican (LUM), fibulin-2 (FBLN2), and latent transforming growth factor beta binding protein 4 (LTBP4) in control human lung tissue. The aim of this study was to examine the expression of these ECM proteins in the airway walls of COPD patients and compare that to controls. <b>Methods:</b> IHC staining of ECM proteins was performed on COPD (stage II-IV, n= 27) and control (ex and current smokers, n= 28) human lung tissue sections. ImageJ was used to quantify the positively stained area and mean intensity of each protein in the airway walls. Regression analyses were performed using linear mixed modelling corrected for age, sex, and smoking status. <b>Results:</b> Both area and intensity of COL1A1 and intensity of LUM staining was lower in COPD airway walls compared to controls. No differences were observed between COPD and controls for the other proteins. <b>Conclusion:</b> COL1A1 and LUM may represent COPD ECM signatures from which an understanding of the pathogenesis may reveal underlying mechanisms of airflow limitation resulting from these airway wall changes. Moreover, studying the specific localization of COL1A1 and LUM expression within the airway walls can provide knowledge about their function in disease processes. Age-associated changes of these ECM proteins in COPD lungs are currently under investigation.