Alterations in the core-matrisome profiles between healthy and COPD lungs

<bold>Background:</bold> COPD is a heterogeneous disease involving different lung compartments. Dysregulation in the ECM, including basement membrane (BM) proteins, is associated with disease progression. Collagens are the main components of the ECM and their biosynthesis and turnover is highly changed in COPD. Alterations in type IV collagen (COLIV), a major component of the BM, its precise arrangement, and distribution of its distinct α-chains remains relatively understudied. <bold>Aim:</bold> To assess changes in the ECM composition, to identify differential distribution of diverse COLIV isoforms and to characterize the site-specific COLIV post-translational modifications following ECM enrichment from donor and COPD lungs. <bold>Methods:</bold> We performed proteomic profiling of the matrisome from decellularized COPD and donor lung by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiplex IF (mIF) was done for compartmental profiling of COLIV α-chains combined with cell-type specific markers. <bold>Results:</bold> We detected 277 matrisomal proteins from the ECM enriched donor and COPD lung. Of these, 130 represented core matrisome proteins, and the remaining matrisome associated proteins including ECM regulators, ECM-affiliated, secreted factors and proteoglycans. We observed significant changes between the matrisome and matrisome-associated proteins in donors in comparison to COPD. mIF showed differential geographic distribution of COLIV α-chains between donotr and COPD. <bold>Conclusion:</bold> A plethora of diverse ECM proteins has been altered in COPD, with a particular focus on those linked to BM. We identified a divergent COLIV α-chain signatures between donor and COPD indicating their potential implications in the progression of COPD.