The lung extracellular matrix protein landscape in severe early-onset and moderate chronic obstructive pulmonary disease.

Joglekar, M. M.; Bekker, N. J.; Koloko Ngassie, M. L.; Vonk, J. M.; Borghuis, T.; Reinders-Luinge, M. A.; Bakker, J.; Woldhuis, R. R.; Pouwels, S. D.; Melgert, B. N.; Timens, W.; Brandsma, C.-A.; Burgess, J. K.

doi:10.1101/2023.10.20.562391

bioRxiv · 10.1101/2023.10.20.562391

The lung extracellular matrix protein landscape in severe early-onset and moderate chronic obstructive pulmonary disease.

Joglekar, M. M.·Bekker, N. J.·Koloko Ngassie, M. L.·Vonk, J. M.·Borghuis, T.·Reinders-Luinge, M. A.·Bakker, J.·Woldhuis, R. R.·Pouwels, S. D.·Melgert, B. N.·Timens, W.·Brandsma, C.-A.·Burgess, J. K.

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Abstract

Extracellular matrix (ECM) remodeling has been implicated in the irreversible obstruction of airways and destruction of alveolar tissue in chronic obstructive pulmonary disease (COPD). Studies investigating differences in the lung ECM in COPD have mainly focused on some collagens and elastin, leaving an array of ECM components unexplored. We investigated the differences in the ECM landscape comparing severe-early onset (SEO-) COPD and moderate COPD to control lung tissue for collagen type I chain 1 (COL1A1), COL6A1, COL6A2, COL14A1, fibulin 2 and 5 (FBLN2, FBLN5), latent transforming growth factor-beta binding protein 4 (LTBP4), lumican (LUM), versican (VCAN), decorin (DCN), and elastin (ELN) using image analysis and statistical modelling. Percentage area and/or mean intensity of expression of LUM in the parenchyma, and COL1A1, FBLN2, LTBP4, DCN, and VCAN in the airway walls, was proportionally lower in COPD compared to controls. Lowered levels of most ECM proteins were associated with decreasing FEV1 measurements, indicating a relationship with disease severity. Furthermore, we identified six unique ECM signatures where LUM and COL6A1 in parenchyma and COL1A1, FBLN5, DCN, and VCAN in airway walls appear essential in reflecting the presence and severity of COPD. These signatures emphasize the need to examine groups of proteins to represent an overall difference in the ECM landscape in COPD, that are more likely to be related to functional effects, than individual proteins. Our study revealed differences in the lung ECM landscape between control and COPD and between SEO and moderate COPD signifying distinct pathological processes in the different subgroups. NEW & NOTEWORTHYOur study identified COPD-associated differences in the lung ECM composition. We highlight the compartmental differences in the ECM landscape in different subtypes of COPD. The most prominent differences were observed for severe-early onset COPD. Moreover, we identified unique ECM signatures that describe airway walls and parenchyma providing insight into the intertwined nature and complexity of ECM changes in COPD that together drive ECM remodeling and may contribute to disease pathogenesis.

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Joglekar, M. M., Bekker, N. J., Koloko Ngassie, M. L., Vonk, J. M., Borghuis, T., Reinders-Luinge, M. A., Bakker, J., Woldhuis, R. R., Pouwels, S. D., Melgert, B. N., Timens, W., Brandsma, C.-A., Burgess, J. K.. 2023-10-20. The lung extracellular matrix protein landscape in severe early-onset and moderate chronic obstructive pulmonary disease.. https://doi.org/10.1101/2023.10.20.562391

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