Abstract:
BACKGROUND:Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not only energy homeostasis but also stress responses, including ROS. Therefore, we sought to investigate the inhibitory role of metformin in lung fibrosis development via modulating TGF-β signaling. METHODS:TGF-β-induced myofibroblast differentiation in lung fibroblasts (LF) was used for in vitro models. The anti-fibrotic role of metfromin was examined in a bleomycin (BLM)-induced lung fibrosis model. RESULTS:We found that TGF-β-induced myofibroblast differentiation was clearly inhibited by metformin treatment in LF. Metformin-mediated activation of AMPK was responsible for inhibiting TGF-β-induced NOX4 expression. NOX4 knockdown and N-acetylcysteine (NAC) treatment illustrated that NOX4-derived ROS generation was critical for TGF-β-induced SMAD phosphorylation and myofibroblast differentiation. BLM treatment induced development of lung fibrosis with concomitantly enhanced NOX4 expression and SMAD phosphorylation, which was efficiently inhibited by metformin. Increased NOX4 expression levels were also observed in FF of IPF lungs and LF isolated from IPF patients. CONCLUSIONS:These findings suggest that metformin can be a promising anti-fibrotic modality of treatment for IPF affected by TGF-β.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Sato N,Takasaka N,Yoshida M,Tsubouchi K,Minagawa S,Araya J,Saito N,Fujita Y,Kurita Y,Kobayashi K,Ito S,Hara H,Kadota T,Yanagisawa H,Hashimoto M,Utsumi H,Wakui H,Kojima J,Numata T,Kaneko Y,Odaka M,Morikawa T,Nadoi
10.1186/s12931-016-0420-xsubject
Has Abstractpub_date
2016-08-30 00:00:00pages
107issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-016-0420-xjournal_volume
17pub_type
杂志文章abstract:BACKGROUND:Secondary pulmonary alveolar septal formation requires platelet derived growth factor (PDGF-A) and platelet derived growth factor receptor-alpha (PDGFRα), and their regulation influences alveolar septal areal density and thickness. Insufficient PDGFRα expression in lung fibroblasts (LF) results in failed sep...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-68
更新日期:2013-07-02 00:00:00
abstract:BACKGROUND:Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants....
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-019-1180-1
更新日期:2019-09-12 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF), the most prevalent idiopathic interstitial pneumonia, is associated with a poor prognosis. An accurate diagnosis of IPF is essential for optimal management. The recent ATS/ERS/JRS/ALAT recommendations on the diagnosis and management of IPF were developed from a systematic review of...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-S1-S2
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1149-0
更新日期:2019-08-06 00:00:00
abstract:BACKGROUND:Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine wh...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0462-0
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-90
更新日期:2011-07-05 00:00:00
abstract:BACKGROUND:Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV). It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs) followed by a shorter inspi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-38
更新日期:2006-03-10 00:00:00
abstract:BACKGROUND:Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01588-6
更新日期:2020-12-10 00:00:00
abstract:BACKGROUND:For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for ...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-8-30
更新日期:2007-04-04 00:00:00
abstract:BACKGROUND:Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01495-w
更新日期:2020-09-03 00:00:00
abstract:BACKGROUND:Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. The...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0265-8
更新日期:2015-09-16 00:00:00
abstract:BACKGROUND:Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjec...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-52
更新日期:2008-07-11 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common manifestation of SSc and a leading cause of death. MAIN BODY:All patients newly diagnosed with SSc should receive a comprehensive clinical evaluation, including asse...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-0980-7
更新日期:2019-01-18 00:00:00
abstract:BACKGROUND:An increasing number of epidemiological and experimental studies have associated exposure to second-hand smoke (SHS) during pregnancy with adverse outcomes in newborns. As we have previously shown in mice, in utero exposure to SHS at critical stages of fetal development, results in altered lung responses and...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0591-0
更新日期:2017-06-27 00:00:00
abstract:BACKGROUND:The collagen gel contraction assay measures gel size to assess the contraction of cells embedded in collagen gel matrices. Using the assay with lung fibroblasts is useful in studying the lung tissue remodeling process in wound healing and disease development. However, the involvement of bronchial epithelial ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0680-0
更新日期:2017-11-22 00:00:00
abstract::The language of science should be objective and detached and should place data in the appropriate context. The aim of this commentary was to explore the notion that recent trends in the use of language have led to a loss of objectivity in the presentation of scientific data. The relationship between the value-laden vo...
journal_title:Respiratory research
pub_type: 社论
doi:10.1186/1465-9921-10-35
更新日期:2009-05-11 00:00:00
abstract:BACKGROUND:Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-82
更新日期:2007-11-15 00:00:00
abstract::Bacillus Calmette-Guérin (BCG) vaccination is routine and near-universal in many low- and middle-income countries (LMIC). It has been suggested that BCG can have a protective effect on COVID-19 morbidity and mortality. This commentary discusses the limitations of the evidence around BCG and COVID-19. We argue that hig...
journal_title:Respiratory research
pub_type: 信件,评审
doi:10.1186/s12931-020-01439-4
更新日期:2020-07-11 00:00:00
abstract:BACKGROUND:Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD:Statistical patterns of subjective and objective findings were assessed by retrospective chart re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-149
更新日期:2005-12-19 00:00:00
abstract:RATIONALE:Gastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01469-y
更新日期:2020-08-03 00:00:00
abstract::MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-144
更新日期:2011-10-31 00:00:00
abstract:BACKGROUND:The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. METHODS:We performed a cross-sectional study comparing subjects with COPD and asthma to subjects ...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/1465-9921-12-127
更新日期:2011-09-27 00:00:00
abstract:BACKGROUND:Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefor...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-127
更新日期:2010-09-21 00:00:00
abstract:BACKGROUND:Mechanical ventilation can cause ventilator-induced lung injury (VILI) and lung fibrosis; however, the underlying mechanisms are still not fully understood. RNA sequencing is a powerful means for detecting vitally important protein-coding transcripts and long non-coding RNAs (lncRNAs) on a genome-wide scale,...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0822-z
更新日期:2018-06-22 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been r...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0408-6
更新日期:2016-07-26 00:00:00
abstract:BACKGROUND:The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. METHODS:CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-128
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:To assess the symptomatic and cost burden among patients initiating long-acting bronchodilator (LABD) therapy and impact of adherence on healthcare resource use and costs. METHODS:This retrospective cohort study identified patients with COPD who were newly prescribed a LABD (long-acting muscarinic antagonis...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0295-2
更新日期:2015-11-16 00:00:00
abstract:BACKGROUND:Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-29
更新日期:2014-03-12 00:00:00
abstract::A new international statement defines usual interstitial pneumonia (UIP) which is a histological and radiological form of idiopathic pulmonary fibrosis (IPF) more precisely than previously. In the diagnosis of IPF, either in high resolution computed tomography (HRCT) a UIP pattern must be present or alternatively spec...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-14-43
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND:It is unclear whether the responses of refractory and common Mycoplasma pneumoniae (MP) pneumonia to macrolides differ. Hence, this study aimed to identify biomarkers that may be used to distinguish refractory and common pneumonias caused by MP in children at hospital admission. METHODS:The study included 1...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1152-5
更新日期:2019-08-23 00:00:00