Search results for "myofibroblast"
showing 10 items of 67 documents
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
2006
Background/Aims In hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice. Methods Transgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed an…
DPP-4 is overexpressed in lung tissue from idiopathic pulmonary patients and activates lung fibroblasts
2020
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible form of fibrotic interstitial lung disease, characterized by uncontrolled fibroblast invasion. Dipeptidyl peptidase-4 (DPP-4)/ glucagon-like peptide 1 (GLP-1) system is involved in multiple effects, including cardiac, liver or kidney fibrosis. However, its implication in IPF has not been described. Objective: To analyse the implication of DPP4/GLP1 system in IPF. Methods: Protein expression of DPP4, GLP-1 and GLP-1 receptor was analyzed in lung tissues from 7 IPF patients. TGFβ1-induced fibroblast to myofibroblast transition (FMT), epithelial to mesenchymal transition (EMT) and mesothelial to mesenchymal trans…
Potential Involvement of Osteopontin in Inflammatory and Fibrotic Processes in Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension
2019
Background Inflammation and incomplete thrombus resolution leading to obstructive fibrotic remodelling are considered critical mechanisms for the development of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE). Osteopontin (OPN) is involved in a variety of biological processes including inflammation and tissue fibrosis. Methods OPN plasma concentrations were measured in 70 CTEPH and 119 PE patients. Tissue material from 6 CTEPH patients removed during pulmonary endarterectomy and murine venous thrombi induced by subtotal ligation of the inferior vena cava in C57BL/6 mice were analysed by (immuno)histochemistry. Results CTEPH patients had higher OPN plasma…
Deformation-induced transitional myofibroblasts contribute to compensatory lung growth
2016
In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection (P < 0.001). Within 3 days of pneumonectomy, …
Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice
2019
Abstract Background Adaptation to aortic valve stenosis leads to myocardial hypertrophy, which has been associated with inflammation, fibrosis and activation of the endocannabinoid system. Since the endocannabinoid system and the CB2 receptor provide cardioprotection and modulate immune response in experimental ischemia, we investigated the role of CB2 in a mouse model of cardiac pressure overload. Methods Transverse aortic constriction was performed in CB2 receptor-deficient (Cnr2−/−) mice and their wild-type littermates (Cnr2+/+). After echocardiography and Millar left heart catheter hemodynamic evaluation hearts were processed for histological, cellular and molecular analyses. Results Th…
Evidence for pleural epithelial-mesenchymal transition in murine compensatory lung growth
2017
In many mammals, including rodents and humans, removal of one lung results in the compensatory growth of the remaining lung; however, the mechanism of compensatory lung growth is unknown. Here, we investigated the changes in morphology and phenotype of pleural cells after pneumonectomy. Between days 1 and 3 after pneumonectomy, cells expressing α-smooth muscle actin (SMA), a cytoplasmic marker of myofibroblasts, were significantly increased in the pleura compared to surgical controls (p < .01). Scanning electron microscopy of the pleural surface 3 days post-pneumonectomy demonstrated regions of the pleura with morphologic features consistent with epithelial-mesenchymal transition (EMT); nam…
HIF-Overexpression and Pro-Inflammatory Priming in Human Mesenchymal Stromal Cells Improves the Healing Properties of Extracellular Vesicles in Exper…
2021
Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have therapeutic potential in the treatment of several immune disorders, including ulcerative colitis, owing to their regenerative and immunosuppressive properties. We recently showed that MSCs engineered to overexpress hypoxia-inducible factor 1-alpha and telomerase (MSC-T-HIF) and conditioned with pro-inflammatory stimuli release EVs (EVMSC-T-HIFC) with potent immunomodulatory activity. We tested the efficacy of EVMSC-T-HIFC to repolarize M1 macrophages (Mφ1) to M2-like macrophages (Mφ2-like) by analyzing surface markers and cytokines and performing functional assays in co-culture, including efferocytosis and T-cel…
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…
The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts.
2009
Introduction Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs' function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown. Methods In this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) on cellular functions of human joint capsule MFs. MFs were challenged w…
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…