Compositional changes of the lung extracellular matrix in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Remodeling of the extracellular matrix (ECM), which is pivotal for 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 post-transplant lungs were obtained from patients with ARDS (n=28) admitted to the University Medical Center Groningen between 2010-2020. 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 (<7days, 7-14days, >14days). 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 >14days duration. These findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology of ARDS during progression.