Biology subjects

Pillay, J.

Publications and source records attributed to Pillay, J..

3 recordsLinked to original sources

bioRxiv2026

Collagen crosslinking and organizational patterns reflect common disease processes in idiopathic pulmonary fibrosis and non-resolving acute respiratory distress syndrome

RationaleFibrotic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and fibroproliferative remodeling in acute respiratory distress syndrome (ARDS), are characterized by increased extracellular matrix (ECM) deposition. However, measuring collagen accumulation alone does not capture differences in ECM organization or biochemical maturation that may distinguish persistent fibrosis from potentially reversible remodeling. ObjectivesTo examine collagen organization characteristics and mature (pyridinoline) collagen crosslinking amount in established end stage fibrotic lung disease (IPF) and fibroproliferation following an acutely damaged lung (non-resolving (NR) ARDS) and to investigate any relationships in these parameters and temporal tissue remodeling. MethodsHuman lung tissue samples from control subjects, patients with IPF, and NR-ARDS were analyzed. Collagen amount and fiber organization were digitally quantified using picrosirius red staining. Mature collagen crosslinking was assessed by quantification of pyridinoline crosslinks. Measurements and Main ResultsLung tissue from both IPF and NR-ARDS lungs had higher collagen content compared with controls. Collagen fiber organization differed between groups. IPF lungs exhibited collagen architectures consistent with established fibrosis, whereas NR-ARDS lungs showed altered but less stabilized collagen organization despite similarly elevated collagen levels. Mature collagen crosslinks were significantly higher in IPF lungs but not in NR-ARDS lungs compared to controls. Integrated analyses identified distinct disease-associated ECM phenotypes, indicating that higher collagen abundance in NR-ARDS, unlike IPF, is not accompanied by more mature and persistent collagen crosslinking. ConclusionsDespite shared increases in collagen content, IPF and NR-ARDS lungs differ fundamentally in collagen organization and crosslinking maturity, suggesting differences in the reversibility of these conditions.

pathology↗

bioRxiv2025

Myeloid cell differentiation within extracorporeal membrane oxygenators in patients with ARDS

Extracorporeal membrane oxygenation is a last-resort rescue therapy for patients with acute respiratory distress syndrome (ARDS). The membrane oxygenator (MO) is prone to coagulation and dysfunction. Studies have shown that circulating cells can be retained within the MO, however, it is unclear what their cellular identity is. Here, we used single cell-RNA sequencing to characterize MO-resident and incoming venous PBMCs from ARDS patients. We find that MO contain both undifferentiated monocytes and differentiated macrophages, characterized by increased SPP1 expression. These results indicate that myeloid retention and differentiation occurs within MO, which might contribute to MO dysfunction.

cell biology↗

bioRxiv2024

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

BackgroundAcute 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 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. MethodsParaffin-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 1 chain (Col IIIa1), IV 3 chain (Col IVa3), VI 1 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. ResultsHigher 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. ConclusionsThese findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology in ARDS during progression.

molecular biology↗