scholarly journals Correlation between sestrin2 expression and airway remodeling in COPD

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Da-Wei Zhang ◽  
Yuan-Yuan Wei ◽  
Shuang Ji ◽  
Guang-He Fei
Keyword(s):  
Airway Remodeling ◽  
Chest Ct ◽  
Chronic Obstructive ◽  
Pathological Changes ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Imaging Characteristics ◽  
Copd Patients ◽  
Staining Methods ◽  
First Time

Abstract Background Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified. Methods A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed. Results In patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT. Conclusion Increased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.

scholarly journals Correlation between sestrin2 expression and airway remodeling in COPD

2020 ◽  
Author(s):  
Da-Wei Zhang ◽  
Yuan-Yuan Wei ◽  
Shuang Ji ◽  
Guang-He Fei
Keyword(s):  
Airway Remodeling ◽  
Chest Ct ◽  
Chronic Obstructive ◽  
Pathological Changes ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Imaging Characteristics ◽  
Copd Patients ◽  
Staining Methods ◽  
First Time

Abstract Background. Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified.Methods. A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed. Results. In patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT.Conclusion. Increased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.

scholarly journals Correlation between sestrin2 expression and airway remodeling in COPD

2020 ◽  
Author(s):  
Da-Wei Zhang ◽  
Yuan-Yuan Wei ◽  
Shuang Ji ◽  
Guang-He Fei
Keyword(s):  
Airway Remodeling ◽  
Chest Ct ◽  
Chronic Obstructive ◽  
Pathological Changes ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Imaging Characteristics ◽  
Copd Patients ◽  
Staining Methods ◽  
First Time

Abstract Background. Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified.Methods. A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed.Results. In patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT.Conclusion. Increased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.

scholarly journals Sestrin2 Was Involved in Airway Remodeling in COPD: A Multi-level Research

2020 ◽  
Author(s):  
Da-Wei Zhang ◽  
Yuan-Yuan Wei ◽  
Shuang Ji ◽  
Guang-He Fei
Keyword(s):  
Airway Remodeling ◽  
Chest Ct ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Pathological Changes ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Imaging Characteristics ◽  
Copd Patients ◽  
Staining Methods

Abstract Background. Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), which is greatly associated with oxidative stress. Sestrin2 has recently drawn attention as a representative antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has not yet been clarified.Methods. A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were showed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was assessed by Immunohistochemistry staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) of all participants were measured for the evaluation of airway remodeling. Serum sestrin2 concentrations' relationship with MMP9 and airway parameters on chest CT was further analyzed. Results. In patients with COPD, staining results of airway structure showed noticeable pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were found on chest CT. Additionally, the serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters on chest CT.Conclusion. Increased expression of sestrin2 is related to airway remodeling in COPD at three levels including histology, biomarkers and imaging. It is demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in COPD.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients

2018 ◽  
Vol 314 (2) ◽  
pp. H180-H187 ◽  
Author(s):  
U. W. Iepsen ◽  
G. W. Munch ◽  
C. K. Ryrsø ◽  
N. H. Secher ◽  
P. Lange ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Copd Patients ◽  
Sympathetic Vasoconstriction ◽  
Functional Sympatholysis ◽  
Healthy Control

Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min−1·kg leg mass−1), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WLmax)], 3) ATP (0.05 µmol·min−1·kg leg mass−1) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min−1·kg leg mass−1). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: −3 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) and 20% WLmax(COPD: −4 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: −0.03 ± 0.01 l·min−1·kg leg mass−1vs. controls: −0.04 ± 0.01 l·min−1·kg leg mass−1, P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained.NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.

scholarly journals Face-to-face Training as an Effective Approach for Instructing Rotahaler Technique in Newly Diagnosed Cases of Asthma and COPD: a Pilot Study

2015 ◽  
Vol 53 (198) ◽  
pp. 150-153 ◽  
Author(s):  
Ramesh Sharma Poudel ◽  
Shakti Shrestha ◽  
Rano Mal Piryani ◽  
Aastha Prajapati ◽  
Dipendra Khatiwada
Keyword(s):  
Chronic Obstructive ◽  
Newly Diagnosed ◽  
Obstructive Pulmonary Disease ◽  
Face To Face ◽  
Copd Patients ◽  
Study Population ◽  
The Mean ◽  
Gina Guidelines ◽  
Keywords Asthma ◽  
First Time

Introduction: This study aimed to evaluate the effectiveness of face-to-face training for instructing rotahaler technique in newly diagnosed cases of asthma and chronic obstructive pulmonary disease. Methods: A hospital-based study was conducted on twenty patients who were prescribed rotahaler for the first time. Patients received face-to-face training on rotahaler technique from pharmacist using GINA guidelines. The patients rotahaler technique was assessed after two weeks of training and scored one for correct and zero for incorrect steps. Descriptive statistics was performed. Results: The mean age of the study population was 48.85±20.49 years. Eleven (55%) patients were females and 13 (65%) were formally uneducated. Fourteen patients (70%) were able to perform all the steps correctly giving overall median score of 8 (7-8). Conclusions: Face-to-face training seems to be effective approach for instructing rotahaler technique in asthma and COPD patients.  Keywords: asthma; COPD; face-to-face training; inhaler technique; pharmacist.

scholarly journals SP-D Polymorphisms and the Risk of COPD

2012 ◽  
Vol 33 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Tania A. Shakoori ◽  
Don D. Sin ◽  
S. Nazim Hussain Bokhari ◽  
Farkhanda Ghafoor ◽  
A. R. Shakoori
Keyword(s):  
Restriction Analysis ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Limited Data ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
First Time

Introduction: There are limited data linking serum levels of surfactant protein D, its genetic polymorphisms to the risk of Chronic Obstructive Pulmonary Disease (COPD).Objectives: We sought to investigate these relationships using a case control study design.Methods: Post bronchodilator values of FEV1/FVC <0.7 were used to diagnose COPD patients (n= 115). Controls were healthy subjects with normal spirometry (n= 106) Single nucleotide polymorphisms (rs721917, rs2243639, rs3088308) were genotyped using polymerase chain reaction (PCR) and restriction analysis. Serum SP-D levels were measured using a specific immunoassay.Results:Allele ‘A’ at rs3088308 (p< 0.00,B= −0.41) and ‘C’ allele at rs721917 (p= 0.03; B = −0.30) were associated with reduced serum SP-D levels. Genotype ‘T/T’ at rs721917 was significantly associated with risk of COPD (p= 0.01). Patients with repeat exacerbations had significantly higher serum SP-D even after adjusting for genetic factors.Conclusions:We report for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirm the previous association of rs721917 to the risk of COPD and serum SP-D levels.

Role of nitric oxide synthase/arginase balance in bronchial reactivity in patients with chronic obstructive pulmonary disease

2008 ◽  
Vol 294 (3) ◽  
pp. L489-L497 ◽  
Author(s):  
Jean-Marc Tadié ◽  
Priscilla Henno ◽  
Ingrid Leroy ◽  
Claire Danel ◽  
Emmanuel Naline ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Resting Tension ◽  
Copd Patients ◽  
Nos2 Expression

Competition between nitric oxide synthases (NOSs) and arginases for their common substrate l-arginine could be involved in the regulation of cholinergic airway reactivity and subsequent airway remodeling. The aims of this study were to evaluate the relationships between the expression of this enzymatic balance and the effects of NOS and arginase inhibition on bronchoconstrictive response to acetylcholine of patients without and with early chronic obstructive pulmonary disease (COPD). Twenty-two human bronchi [15 COPD (9 GOLD-0, 6 GOLD-1, -2-A), 7 nonsmokers] were investigated for immunohistochemistry and modulation of acetylcholine-induced airway constriction. Significantly increased expression of NOS2 in immunoblots of bronchial tissue and staining in smooth muscle cells was evidenced in patients with COPD compared with control subjects, whereas no modification of arginase expression was evidenced. Forced expiratory volume in 1 s (FEV1) and NOS2 expression were negatively correlated (ρ = −0.54, P = 0.027). Pharmacological experiments demonstrated that resting tension was elevated in COPD compared with control subjects (2,243 ± 154 vs. 1,574 ± 218 mg, P = 0.03) and was positively correlated with the expression of NOS2 (ρ = 0.61, P = 0.044), whereas constrictor response to acetylcholine was similar [active tension, sensitivity (−logEC10), and reactivity (slope)]. The sole effect of the specific arginase inhibitor Nω-hydroxy-nor-l-arginine (1 μM) was to decrease sensitivity in COPD patients, whereas 1 mM NG-nitro-l-arginine methyl ester unexpectedly decreased resting tension because of a non-cGMP-dependent effect. In conclusion, an upregulation of NOS2 expression in COPD patients is involved in airway tone regulation and functional airflow limitation, whereas increased arginase activity is involved in airway sensitivity.

scholarly journals Relationship Between Circulating Serpina3g, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinase-1 and -2 with Chronic Obstructive Pulmonary Disease Severity

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 62 ◽  
Author(s):  
Pelin Uysal ◽  
Hafize Uzun
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Matrix Metalloproteinase ◽  
Pulmonary Disease ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Chronic Obstructive ◽  
Tissue Inhibitor ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Copd Patients ◽  
Metalloproteinase 9

Chronic obstructive pulmonary disease (COPD) is influenced by genetic and environmental factors. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. Here, we examined the relationship between circulating serpina3g, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1 and -2, respectively) and severity of COPD. We included 150 stable COPD patients and 35 control subjects in the study. The COPD patients were classified into four groups (I, II, III, and IV), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines based on the severity of symptoms and the exacerbation risk. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in the all patients than in control subjects. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in groups III and IV than in groups I and II. A negative correlation between serpina3g, MMP-9, and TIMP-1 and -2 levels and the forced expiratory volume in 1 s (FEV1) was observed. MMP-9 concentration and the MMP-9/TIMP-1 ratio were higher in patients with emphysema than in other phenotypes (both with p < 0.01). The findings of this study suggest that circulating serpina3g, MMP-9, and TIMP-1 and -2 levels may play an important role in airway remodeling in COPD pathogenesis. Disrupted protease-antiprotease imbalance in patients with COPD is related to the presence of airway injury. MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors of emphysema in COPD patients.

scholarly journals Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease

2018 ◽  
Vol 132 (14) ◽  
pp. 1615-1627 ◽  
Author(s):  
Mathew S. Eapen ◽  
Anudeep Kota ◽  
Howard Vindin ◽  
Kielan D. McAlinden ◽  
Dia Xenaki ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Smooth Muscle ◽  
Pulmonary Disease ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Mitogen Activated Protein Kinase ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD.

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