scholarly journals The Correlation between FSTL1 Expression and Airway Remodeling in Asthmatics

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yahui Liu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Tao Li ◽  
Xingai Jiao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bronchoalveolar Lavage Fluid ◽  
Airway Remodeling ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Impulse Oscillometry ◽  
Rank Analysis ◽  
Blood Tests ◽  
Extracellular Glycoprotein

Background. Asthma is characterized by airway remodeling. Follistatin-like protein 1 (FSTL1) is an extracellular glycoprotein. Recent studies suggest that FSTL1 may participate in the pathogenesis of asthma. Objectives. To analyze the association between FSTL1 and some parameters and inspect the role of FSTL1 in asthma. Methods. We examined FSTL1 levels in 32 asthmatics and 25 controls. All subjects enrolled had routine blood tests, spirometry, and impulse oscillometry performed. Additionally, 15 of the 32 asthmatics underwent fibre optic bronchoscopy. Spearman rank analysis was performed to detect the correlation between FSTL1 and other parameters. Results. Plasma FSTL1 levels were higher in asthmatics (130.762 ± 46.029 ng/mL) than in controls (95.408 ± 33.938 ng/mL) (p=0.009). Plasma FSTL1 levels were associated with fibrosis levels around the airways (rs=0.529, p=0.043) and α-smooth muscle actin (α-SMA) (rs=0.554, p=0.032). FSTL1 levels in bronchoalveolar lavage fluid were associated with collagen I (rs=0.536, p=0.040), α-SMA (rs=0.561, p=0.029), fibrosis levels (rs=0.779, p=0.001), and the thickness of the airway reticular basement membrane (RBM) (rs=0.660, p=0.007). Conclusions. FSTL1 levels in asthmatics were linked with increased smooth muscle mass and thickened RBM. FSTL1 may contribute to airway remodeling in asthmatics.

scholarly journals S1PR2 Inhibition Attenuates Allergic Asthma Possibly by Regulating Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Hanye Liu ◽  
Liangchang Li ◽  
Zhengai Chen ◽  
Yilan Song ◽  
Weidong Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Airway Remodeling ◽  
Lavage Fluid ◽  
Expression Levels ◽  
Sphingosine 1 Phosphate ◽  
Masson Staining

This study is to investigate the role of Sphingosine-1-phosphate (S1P) in the asthma progression, and the involvement of autophagy. Airway remodeling mice were subjected to the HE, PAS, and Masson staining. Protein expression levels in the tissues, samples and model cells were detected with ELISA, Western blot analysis, and immunohistochemical/immunofluorescent analysis. The S1P2 receptor antagonist JTE-013 decreased the inflammatory cell infiltration and goblet cell production in asthmatic mice tissues. The IL-1, IL-4, IL-5 and serum IgE contents were decreased in bronchoalveolar lavage fluid, while the Beclin1 expression in lung tissues was decreased. The LC3B1 to LC-3B2 conversion was decreased, with increased P62 accumulation and decreased p-P62 expression. In airway remodeling mice, JTE-013 significantly decreased collagen deposition in lung tissues and decreased smooth muscle cell smooth muscle activating protein expression. In lung tissue, the expression levels of Beclin1 were decreased, with decreased LC3B1 to LC-3B2 conversion, as well as the increased P62 accumulation and decreased p-P62 expression. However, these effects were reversed by the RAC1 inhibitor EHT 1864. Similar results were observed for the silencing of S1P2 receptor in the cells, as shown by the decreased Beclin1 expression, decreased LC3B1 to LC-3B2 conversion, increased P62 accumulation, and decreased p-P62 expression. The smooth muscle activators were significantly decreased in the JTE-013 and EHT1864 groups, and the EHT 1864 + S1P2-SiRNA expression level was increased. S1P is involved in the progression of asthma and airway remodeling, which may be related to the activation of S1PR2 receptor and inhibition of autophagy through RAC1.

scholarly journals Crucial Role of Extracellular Vesicles in Bronchial Asthma

2019 ◽  
Vol 20 (10) ◽  
pp. 2589 ◽  
Author(s):  
Tatsuya Nagano ◽  
Masahiro Katsurada ◽  
Ryota Dokuni ◽  
Daisuke Hazama ◽  
Tatsunori Kiriu ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Extracellular Vesicles ◽  
Bronchoalveolar Lavage Fluid ◽  
Cell Types ◽  
Lavage Fluid ◽  
Generation Process ◽  
Intracellular Proteins ◽  
Novel Biomarkers ◽  
Microarray Analyses

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

scholarly journals Role of TNFR1 in the innate airway hyperresponsiveness of obese mice

2012 ◽  
Vol 113 (9) ◽  
pp. 1476-1485 ◽  
Author(s):  
Ming Zhu ◽  
Alison S. Williams ◽  
Lucas Chen ◽  
Allison P. Wurmbrand ◽  
Erin S. Williams ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Tumor Necrosis Factor Receptor ◽  
Lavage Fluid ◽  
Forced Oscillation Technique ◽  
Obese Mice ◽  
Wild Type ◽  
Necrosis Factor

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

scholarly journals Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation

2016 ◽  
Vol 40 (5) ◽  
pp. 895-907 ◽  
Author(s):  
Yi Ji ◽  
Siyuan Chen ◽  
Bo Xiang ◽  
Yuan Li ◽  
Li Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Growth Arrest ◽  
Notch Signaling Pathway ◽  
Cell Growth Arrest ◽  
Muscle Myosin ◽  
Dependent Mechanism

Background: The Notch signaling pathway has been implicated in the pericyte phenotype, but its exact roles in hemangioma-derived pericytes (Hem-pericytes) remain ill defined. Methods: Hem-pericytes were stimulated by immobilized recombinant Jagged1. The potential mechanisms of Notch-induced Hem-pericytes growth arrest were investigated by cell cycle assay, and the role of the Notch in promoting Hem-pericyte maturation was also analyzed by real-time PCR and western blot. Results: Activation of Notch3 in Hem-pericytes significantly reduced cell proliferation and inhibited cell cycle transition. This event was associated with an increase in the levels of p21Cip1. Knockdown of p21Cip1 resulted in a significant rescue of Notch-induced cell growth arrest and an entry into the cell cycle. We showed that Jagged1 activation of Notch3 signaling upregulated the expression of the pericyte contractile markers smooth muscle myosin heavy chain (smMHC) and α-smooth muscle actin (αSMA), concomitant with an increase in the expression of myocardin in Hem-pericytes. We further revealed that the endothelial-derived Jagged1 modulated the Hem-pericyte phenotype via a contact-dependent mechanism. Conclusions: Our results demonstrated that Jagged1 activation of Notch3 resulted in a significant decrease in cell proliferation while concomitantly promoting Hem-pericyte maturation. These data provide initial evidence that Notch induces a quiescent phenotype in Hem-pericytes.

scholarly journals The Role of Thoracic Ultrasonography and Airway Endoscopy in the Diagnosis of Equine Asthma and Exercise-Induced Pulmonary Hemorrhage

2021 ◽  
Vol 8 (11) ◽  
pp. 276
Author(s):  
Chiara Maria Lo Feudo ◽  
Luca Stucchi ◽  
Elena Alberti ◽  
Giovanni Stancari ◽  
Bianca Conturba ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Hemorrhage ◽  
Lavage Fluid ◽  
Lymphoid Hyperplasia ◽  
Inflammatory Status ◽  
Equine Asthma ◽  
Exercise Induced ◽  
Tracheal Mucus ◽  
Tracheal Bifurcation

Mild-moderate (MEA), severe (SEA) equine asthma and exercise-induced pulmonary hemorrhage (EIPH) are common respiratory disorders in horses. The present retrospective study aims to evaluate the role of ultrasonography and endoscopy in the diagnosis of these conditions. Three hundred and three horses were included and divided into SEA, MEA and MEA + EIPH groups, on the basis of history, clinical examination and bronchoalveolar lavage fluid (BALf) cytology; scores were assigned to lung ultrasonography, pharyngeal lymphoid hyperplasia (PLH), tracheal mucus (TM) and tracheal bifurcation edema (TB). These scores were compared between groups, and their associations with age, BALf cytology, tracheal wash microbiology and between endoscopic and ultrasonographic scores were statistically analyzed. Ultrasonographic scores were higher in the SEA and MEA + EIPH groups and associated with increased BALf neutrophils and hemosiderophages. The PLH score was higher in younger horses affected by MEA and EIPH and associated with increased eosinophils and hemosiderophages. TM and TB scores were greater in older horses affected by SEA, associated with increased neutrophils and inversely correlated with hemosiderophages. Moreover, TM grade was negatively correlated with mast cells. Thoracic ultrasonography and airway endoscopy can provide useful information about the inflammatory status of upper and lower airways in the horse.

scholarly journals 2045 The role of TGFβ in driving early cystic fibrosis lung disease

2018 ◽  
Vol 2 (S1) ◽  
pp. 33-33
Author(s):  
Elizabeth L. Kramer ◽  
William Hardie ◽  
Kristin Hudock ◽  
Cynthia Davidson ◽  
Alicia Ostmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Transforming Growth Factor ◽  
Genetic Modifier ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Patient Specific

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

scholarly journals HDAC8 inhibition ameliorates pulmonary fibrosis

2019 ◽  
Vol 316 (1) ◽  
pp. L175-L186 ◽  
Author(s):  
Shigeki Saito ◽  
Yan Zhuang ◽  
Takayoshi Suzuki ◽  
Yosuke Ota ◽  
Marjorie E. Bateman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Smooth Muscle Actin ◽  
Lung Fibroblasts ◽  
Peroxisome Proliferator ◽  
Collagen Gels ◽  
Cell Contractility

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)β1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFβ1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFβ1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFβ1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFβ1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.

Role of Alpha-Smooth Muscle Actin and Fibroblast Activation Protein Alpha in Ovarian Neoplasms

2018 ◽  
Vol 83 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Ana Carolinne da Silva ◽  
Millena Prata Jammal ◽  
Renata Margarida Etchebehere ◽  
Eddie Fernando Candido Murta ◽  
Rosekeila Simões Nomelini
Keyword(s):  
Smooth Muscle ◽  
Ovarian Neoplasms ◽  
Smooth Muscle Actin ◽  
Fibroblast Activation Protein ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Fibroblast Activation ◽  
Fibroblast Activation Protein Alpha
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