YiWen Fan, Jill Moser, Rianne M Jongman, Theo Borghuis, Judith M Vonk, Wim Timens, Matijs van Meurs, Janesh Pillay, Janette K Burgess
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引用次数: 0
Abstract
Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Although pulmonary injury initiates alveolar-capillary barrier damage in ARDS, remodeling of the extracellular matrix (ECM), which is pivotal for both tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated the compositional changes in the ECM in different DAD stages in ARDS. Paraffin-embedded lung sections collected during autopsy or from posttransplant lungs were obtained from patients with ARDS (n = 28) admitted to the University Medical Center Groningen between 2010 and 2020. Sections were stained histochemically, and immunohistochemically for collagen III α1 chain (Col IIIa1), IV α3 chain (Col IVa3), VI α1 chain (Col VIa1), periostin (PSTN), lumican (LUM), and fibronectin (FN). The sections were divided into 118 regions based on DAD stages (54 early vs. 64 advanced). The differences in the expression of selected proteins were compared between DAD stages or across ARDS duration (<7 days, 7-14 days, and >14 days). The fiber pattern of Col VIa1 was analyzed using CellProfiler. Higher tissue density, lower proportional areas of Col IIIa1, Col IVa3, and LUM, and more concentrated Col VIa1 fibers were observed in the advanced DAD stage than in the early DAD stage. Areas with higher proportions of total collagen and FN, and lower proportional areas of Col IIIa1, Col IVa3, and LUM were detected in lung regions from patients with ARDS >14-days duration. These findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology in ARDS during progression.NEW & NOTEWORTHY Our study revealed ECM protein compositional differences in lung parenchyma between stages of DAD. In advanced DAD, tissue density was higher, but collagen type III, type IV, and lumican were proportionally lower compared with early DAD. The organization of collagen type VI fibers was highly concentrated in advanced DAD. Our results indicate that both composition and organization of ECM were remodeled in advanced DAD, suggesting a role in manifesting acute respiratory distress syndrome.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.