Regional and disease specific human lung extracellular matrix composition.

Autor: Hoffman ET; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA. Electronic address: Daniel.weiss@med.uvm.edu., Uhl FE; Department of Experimental Medical Science, Lund University, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden., Asarian L; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA., Deng B; Department of Biology, University of Vermont, Burlington, VT, 05405, USA., Becker C; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA., Uriarte JJ; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, 40506, USA., Downs I; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA., Young B; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA., Weiss DJ; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2023 Feb; Vol. 293, pp. 121960. Date of Electronic Publication: 2022 Dec 24.
DOI: 10.1016/j.biomaterials.2022.121960
Abstrakt: Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), are characterized by regional extracellular matrix (ECM) remodeling which contributes to disease progression. Previous proteomic studies on whole decellularized lungs have provided detailed characterization on the impact of COPD and IPF on total lung ECM composition. However, such studies are unable to determine the differences in ECM composition between individual anatomical regions of the lung. Here, we employ a post-decellularization dissection method to compare the ECM composition of whole decellularized lungs (wECM) and specific anatomical lung regions, including alveolar-enriched ECM (aECM), airway ECM (airECM), and vasculature ECM (vECM), between non-diseased (ND), COPD, and IPF human lungs. We demonstrate, using mass spectrometry, that individual regions possess a unique ECM signature characterized primarily by differences in collagen composition and basement-membrane associated proteins, including ECM glycoproteins. We further demonstrate that both COPD and IPF lead to alterations in lung ECM composition in a region-specific manner, including enrichment of type-III collagen and fibulin in IPF aECM. Taken together, this study provides methodology for future studies, including isolation of region-specific lung biomaterials, as well as a dataset that may be applied for the identification of novel ECM targets for therapeutics.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel J. Weiss reports financial support was provided by University of Vermont. Daniel J. Weiss reports a relationship with National Heart Lung and Blood Institute that includes: funding grants. None to declare.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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