Airway inflammation is accompanied by structural changes, termed remodeling, that lead to lung dysfunction over the long term. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. In this study, we examined the effects of leukotriene (LT) D(4) on the function of ET-1-primed fibroblasts. ET-1 at 10(-7) M up-regulated the expression of the CysLT receptors at both the mRNA and protein levels in human lung fibroblasts. LTD(4) enhanced matrix metalloproteinase-2 and pro-collagen production, and alpha-smooth muscle actin expression of ET-1-primed fibroblasts, but had little or no effect on unprimed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD(4). Our data suggested that LTD(4) may act as a precipitating factor during ET-1-mediated airway remodeling and that CysLT1 receptor antagonists may have a role in preventing aberrant extracellular matrix degradation.
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http://dx.doi.org/10.1016/j.clim.2007.05.018 | DOI Listing |
Environ Epigenet
January 2025
Institute of Human Genetics, School of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Fine particulate matter (PM), an atmospheric pollutant that settles deep in the respiratory tract, is highly harmful to human health. Despite its well-known impact on lung function and its ability to exacerbate asthma, the molecular basis of this effect is not fully understood. This integrated transcriptomic and epigenomic data analysis from publicly available datasets aimed to determine the impact of PM exposure and its association with asthma in human airway epithelial cells.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
January 2025
University of Alabama at Birmingham, Medicine, Birmingham, Alabama, United States;
Sci Adv
January 2025
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.
View Article and Find Full Text PDFMol Ther
January 2025
Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia. Electronic address:
Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Otolaryngology, Nationwide Children's Hospital, Columbus, United States of America.
Surgery of the tracheobronchial tree carries high morbidity, with over half of the complications occurring at the anastomosis. Although fibroblasts are crucial in airway wound healing, the underlying cellular and molecular mechanisms in airway reconstruction remain unknown. We hypothesized that airway reconstruction initiates a surgery-induced stress (SIS) response, altering fibroblast communication within airway tissues.
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