Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

Abstract

Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke–induced (CS-induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. Fbln1c−/− mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

“…BALB/c mice were exposed to either normal air (Air) or cigarette smoke (Smk) for 8 weeks. The Smk group develops hallmark features of COPD as previously described (27,28,(32)(33)(34)(35)39). Mice were then infected with IAV A/PR/8/34, and viral titers, airway inflammation (histopathological score), and inflammatory and antiviral cytokines were determined at 7 days postinfection (dpi) (Figure 2A).…”

“…In vivo. Experimental COPD and influenza infection were induced; miR-125a and -b were inhibited using specific antagomirs; and histopathology, IHC, immunoblotting, and cytometric bead array and data analyses were performed as previously described and/or as in Supplemental Methods (33,35,39,(59)(60)(61)(62)(63)(64)(65)(66)(67).…”

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

“…For histological analysis, lung tissue was fixed in formalin prior to mounting, sectioning, and staining with H&E for assessment of lung histopathology and emphysema. For analysis of airway remodeling, the thickness of the epithelial layer was measured in airways with a basement membrane perimeter < 1,000 μm (14,19). Area of collagen deposition around these airways was quantified using Masson's trichrome-stained lung sections with ImageJ software (NIH) and color deconvolution processing (15,19,75).…”

Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties

“…Importantly, there are set of recommendations been laid down by The European Respiratory Society (ERS) which clearly explains the major causes of the variability and the strategies to overcome these variabilities [43], as well as various methods to perform BAL [44,45]. The various solution and media generally employed for collecting BALf include normal sterile saline (0.9% NaCl) [46]/phosphate buffer saline (PBS) [47,48] and Hanks buffered salt solution (HBSS) [49]. Also, the volume and number of aliquots employed for BAlf varies from one study to another, ranging from 500 µl [47] to 1000 µl [49].…”

“…The various solution and media generally employed for collecting BALf include normal sterile saline (0.9% NaCl) [46]/phosphate buffer saline (PBS) [47,48] and Hanks buffered salt solution (HBSS) [49]. Also, the volume and number of aliquots employed for BAlf varies from one study to another, ranging from 500 µl [47] to 1000 µl [49]. All these parameters need to be thoroughly considered based on the previously reported studies to ensure the reproducibility and accuracy of the BALf technique.…”