Search results for "pulmonary fibrosis"
showing 10 items of 95 documents
MUC16 Is Overexpressed in Idiopathic Pulmonary Fibrosis and Induces Fibrotic Responses Mediated by Transforming Growth Factor-β1 Canonical Pathway
2021
Several transmembrane mucins have demonstrated that they contribute intracellularly to induce fibrotic processes. The extracellular domain of MUC16 is considered as a biomarker for disease progression and death in IPF patients. However, there is no evidence regarding the signalling capabilities of MUC16 that contribute to IPF development. Here, we demonstrate that MUC16 was overexpressed in the lung tissue of IPF patients (n = 20) compared with healthy subjects (n = 17) and localised in fibroblasts and hyperplastic alveolar type II cells. Repression of MUC16 expression by siRNA-MUC16 transfection inhibited the TGF-β1-induced fibrotic processes such as mesenchymal/ myofibroblast transformati…
Upregulation of activin-B and follistatin in pulmonary fibrosis: a translational study using human biopsies and a specific inhibitor in mouse fibrosi…
2014
Background: Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. Methods: We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. Results: Activin-B and follistatin mRNA levels…
Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutatio…
2015
Background Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypoh…
Vascular effects of sildenafil in patients with pulmonary fibrosis and pulmonary hypertension: an ex vivo/in vitro study
2015
Sildenafil improves the 6-min walking distance in patients with idiopathic pulmonary fibrosis (IPF) and right-sided ventricular systolic dysfunction.We analysed the previously unexplored role of sildenafil on vasoconstriction and remodelling of pulmonary arteries from patients with IPF and pulmonary hypertension (PH) ex vivo. Pulmonary arteries from 18 donors without lung disease, nine IPF, eight PH+IPF and four PH patients were isolated to measure vasodilator and anti-contractile effects of sildenafil in isometric organ bath. Ventilation/perfusion was explored in an animal model of bleomycin lung fibrosis.Sildenafil relaxed serotonin (5-HT) pre-contracted pulmonary arteries in healthy dono…
MUC1 intracellular bioactivation mediates lung fibrosis
2019
BackgroundSerum KL6/mucin 1 (MUC1) has been identified as a potential biomarker in idiopathic pulmonary fibrosis (IPF), but the role of MUC1 intracellular bioactivation in IPF is unknown.ObjectiveTo characterise MUC1 intracellular bioactivation in IPF.Methods and resultsThe expression and phosphorylation of Thr41 and Tyr46 on the intracellular MUC1-cytoplasmic tail (CT) was increased in patients with IPF (n=22) compared with healthy subjects (n=21) and localised to fibroblasts and hyperplastic alveolar type II cells. Transforming growth factor (TGF)-β1 phosphorylated SMAD3 and thereby increased the phosphorylation of MUC1-CT Thr41 and Tyr46 in lung fibroblasts and alveolar type II cells, ac…
Assessment of Lung Cancer Development in Idiopathic Pulmonary Fibrosis Patients Using Quantitative High-Resolution Computed Tomography:A Retrospectiv…
2020
Purpose The purpose of this study was to investigate histogram-based quantitative high-resolution computed tomography (HRCT) indexes in the assessment of lung cancer (LC) development in idiopathic pulmonary fibrosis (IPF) patients. Materials and methods From IPF databases of 2 national respiratory centers, we retrospectively studied patients with and without LC development-respectively, divided into Group A (n=16) and Group B (n=33). The extent of fibrotic disease was quantified on baseline and follow-up HRCT examinations using kurtosis, skewness, percentage of high attenuation area (HAA%), and percentage of fibrotic area (FA%). These indexes were compared between the 2 groups using the Man…
Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats
2003
Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N ‐acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol·kg−1·day−1) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg−1) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257±323 and 3,200±192 µg·lung−1 in vehicle- and NAC…
Alterations of the beneficial effect of deep inspiration in scleroderma: relationships between lung function and imaging.
2007
<i>Background:</i> It has been postulated that the beneficial effects of deep inspiration are dependent on the magnitude of airway distension by virtue of airway to parenchyma interdependence. <i>Objective:</i> This study was designed to examine whether the changes that occur in pulmonary fibrosis affect the beneficial effect of deep inspiration. <i>Methods:</i> Thirty-one subjects with scleroderma underwent lung volume and diffusion capacity assessment as well as high-resolution computed tomography. To assess the effect of deep inspiration, each subject underwent methacholine provocations in the absence of deep breaths. When the targeted change in lung f…
Attenuation by oralN-acetylcysteine of bleomycin-induced lung injury in rats
2001
Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect ofN-acetylcysteine (NAC) on bleomycin-induced lung fibrosis in rats.NAC (3 mmol·kg−1; oral) was given daily from 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg−1) or saline, until 14 days postinstillation.NAC partially decreased the augmented collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,354±386 and 3,416±326 µg·lung−1in vehicle-treated and NAC-treated rats, respectively; p<0.05). The histological assessment using a semiquantitative score showed less collagen deposition and inflammatory…
Role of tetrahydrobiopterin in pulmonary vascular remodelling associated with pulmonary fibrosis
2013
[Background]: Pulmonary hypertension in idiopathic pulmonary fibrosis (IPF) is indicative of a poor prognosis. Recent evidence suggests that tetrahydrobiopterin (BH4), the cofactor of nitric oxide synthase (NOS), is involved in pulmonary hypertension and that pulmonary artery endothelial-to-mesenchymal transition (EnMT) may contribute to pulmonary fibrosis. However, the role of BH4 in pulmonary remodelling secondary to pulmonary fibrosis is unknown. This study examined the BH4 system in plasma and pulmonary arteries from patients with IPF as well as the antiremodelling and antifibrotic effects of the BH4 precursor sepiapterin in rat bleomycin-induced pulmonary fibrosis and in vitro EnMT mod…