scholarly journals SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD

2013 ◽  
Vol 305 (9) ◽  
pp. L615-L624 ◽  
Author(s):  
Hongwei Yao ◽  
Jae-woong Hwang ◽  
Isaac K. Sundar ◽  
Alan E. Friedman ◽  
Michael W. McBurney ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Transgenic Mice ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Tissue Inhibitor ◽  
Obstructive Pulmonary Disease ◽  
Matrix Metalloproteinase 1 ◽  
Copd Patients ◽  
Lysine Residues

Sirtuin1 (SIRT1), a protein/histone deacetylase, protects against the development of pulmonary emphysema. However, the molecular mechanisms underlying this observation remain elusive. The imbalance of tissue inhibitor of matrix metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. We hypothesized that SIRT1 protects against emphysema by redressing the imbalance between MMPs and TIMPs. To test this hypothesis, SIRT1-deficient and overexpressing/transgenic mice were exposed to cigarette smoke (CS). The protein level and activity of MMP-9 were increased in lungs of SIRT1-deficient mice exposed to CS compared with wild-type (WT) littermates, and these effects were attenuated by SIRT1 overexpression. SIRT1 deficiency decreased the level of TIMP-1, which was augmented in SIRT1 transgenic mice compared with WT littermates by CS. However, the level of MMP-2, MMP-12, TIMP-2, TIMP-3, or TIMP-4 was not altered by SIRT1 in response to CS exposure. SIRT1 reduction was associated with imbalance of TIMP-1 and MMP-9 in lungs of smokers and COPD patients. Mass spectrometry and immunoprecipitation analyses revealed that TIMP-1 acetylation on specific lysine residues was increased, whereas its interaction with SIRT1 and MMP-9 was reduced in mouse lungs with emphysema, as well as in lungs of smokers and COPD patients. SIRT1 deficiency increased CS-induced TIMP-1 acetylation, and these effects were attenuated by SIRT1 overexpression. These results suggest that SIRT1 protects against COPD/emphysema, in part, via redressing the TIMP-1/MMP-9 imbalance involving TIMP-1 deacetylation. Thus redressing the TIMP-1/MMP-9 imbalance by pharmacological activation of SIRT1 is an attractive approach in the intervention of COPD.

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 Reference ranges of matrix metalloproteinase-1, -2, -9 and tissue inhibitor of matrix metalloproteinases-1 concentrations in amniotic fluid in physiological pregnancy

2016 ◽  
Vol 62 (1) ◽  
pp. 96-98
Author(s):  
Yu.V. Korenovsky ◽  
O.V. Remneva
Keyword(s):  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Amniotic Fluid ◽  
Reference Values ◽  
Reference Ranges ◽  
Tissue Inhibitor ◽  
Protein Ratio ◽  
Matrix Metalloproteinase 1 ◽  
Term Labor ◽  
First Stage Of Labor

The aim of this study was to determine reference values of matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in the amniotic fluid at the first stage of labor in physiological pregnancy. 89 women at the first stage of term labor have been examined. Samples of amniotic fluid were taken at the first period of labor by vaginal amniotomy. Concentrations ofMMP-1, MMP-2, MMP-9, and TIMP-1 were investigated in amniotic fluid by ELISA kits. We have determined normal concentration ranges for MMP-1, MMP-2, MMP-9, TIMP-1, and ratios of concentrations of MMPs and TIMP-1 (MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-9/TIMP-1) in the amniotic fluid at the first period of labor in physiological pregnancy. These included: MMP-1 - 5.1-16.8 pg/mg of protein, MMP-2 - 238.3-374.1 pg/mg of protein, MMP-9 - 66.1-113.3 pg/mg of protein, TIMP-1 - 4.7-13.6 pg/mg of protein, ratio of MMP-1/TIMP-1 - 0.1-2.2, ratio of MMP-2/TIMP-1 - 19.9-55.7, ratio of MMP-9/TIMP-1 - 4.2-17.2.

Transgenic expression of matrix metalloproteinase-9 causes adult-onset emphysema in mice associated with the loss of alveolar elastin

2008 ◽  
Vol 294 (6) ◽  
pp. L1149-L1157 ◽  
Author(s):  
Robert Foronjy ◽  
Takwi Nkyimbeng ◽  
Alison Wallace ◽  
Jincy Thankachen ◽  
Yasunori Okada ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Matrix Metalloproteinase ◽  
Chronic Obstructive ◽  
Alveolar Wall ◽  
Littermate Control ◽  
Obstructive Pulmonary Disease ◽  
Transgenic Expression ◽  
Air Space ◽  
Mean Linear Intercept ◽  
Metalloproteinase 9

Matrix metalloproteinase (MMP)-9 has been consistently identified in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, its role in the development of the disease remains undefined. Mice that specifically express human MMP-9 in their macrophages were generated, and morphometric, biochemical, and histological analyses were conducted on the transgenic and littermate control mice over 1 yr to determine the effect of macrophage MMP-9 expression on emphysema formation and lung matrix content. Lung morphometry was normal in transgenic mice at 2 mo of age (mean linear intercept = 50 ± 3 littermate mice vs. 51 ± 2 transgenic mice). However, after 12 mo of age, the MMP-9 transgenic mice developed significant air space enlargement (mean linear intercept = 53 ± 3 littermate mice vs. 61 ± 2 MMP-9 transgenic mice; P < 0.04). Lung hydroxyproline content was not significantly different between wild-type and transgenic mice, but MMP-9 did significantly decrease alveolar wall elastin at 1 yr of age (4.9 ± 0.3% area of alveolar wall in the littermate mice vs. 3.3 ± 0.3% area of alveolar wall in the MMP-9 mice; P < 0.004). Thus these results establish a central role for MMP-9 in the pathogenesis of this disease by demonstrating that expression of this protease in macrophages can alter the extracellular matrix and induce progressive air space enlargement in mice.

Serum matrix metalloproteinases and tympanosclerosis

2010 ◽  
Vol 125 (2) ◽  
pp. 142-146 ◽  
Author(s):  
H Aslan ◽  
M Sinan Başoğlu ◽  
B Şentürk ◽  
C Özbay ◽  
H Katilmiş ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Otitis Media ◽  
Disease Process ◽  
Chronic Otitis Media ◽  
Control Group ◽  
Success Rates ◽  
Tissue Inhibitor ◽  
Matrix Metalloproteinase 1 ◽  
Significant Difference

AbstractAim:To investigate levels of matrix metalloproteinases 2 and 9, and of their tissue inhibitor (i.e. tissue inhibitor matrix metalloproteinase 1), in the serum of patients with tympanosclerosis.Materials and method:We included 40 patients (age range 13–63 years) who had undergone surgery in the ENT department of İzmir Atatürk Training and Research Hospital between 2002 and 2007. Twenty had uncomplicated chronic otitis media and 20 had tympanosclerosis. We also included as the control group 20 individuals with no history of previous otic complaints or systemic or infectious disease. Serum levels of serum matrix metalloproteinases 2 and 9 and of tissue inhibitor matrix metalloproteinase 1 were measured in all subjects and compared.Result:Significantly higher levels of serum matrix metalloproteinases 2 and 9 were found in the tympanosclerosis group, compared with the chronic otitis media and control groups. There was no statistically significant difference in tissue inhibitor matrix metalloproteinase 1 level between the three groups.Conclusion:Tympanosclerosis surgery has poor success rates, since the pathological process is still active. We suggest that high levels of matrix metalloproteinases may play a role in the continuation of the disease process.

scholarly journals Identification of Molecular Mechanisms Underlying Sex-Associated Differences in the Chronic Obstructive Pulmonary Disease through Bioinformatics Analysis

2021 ◽  
Author(s):  
Fengshou Chen ◽  
Haijia Hou ◽  
Jie Han ◽  
Bing Tang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Chronic Obstructive ◽  
Hub Genes ◽  
Obstructive Pulmonary Disease ◽  
P53 Signaling ◽  
Copd Patients ◽  
P53 Signaling Pathway

Abstract Background Accumulating evidence suggests the existence sex associated differences in the Chronic Obstructive Pulmonary Disease (COPD). However, limited knowledge exists on the molecular mechanisms underlying sex associated differences in COPD patients. Methods The GSE8581 dataset obtained from the GEO database was used to analyze differentially expressed genes (DEGs). Then enrichment analysis for DEGs were conducted through Metascape. PPI and the hub genes-pathway networks were constructed using the STRING database and Cytoscape software. Finally, the CTD was used to examine the relationships between the hub DEGs and COPD. Results The results revealed that different subsets of DEGs had different characteristics in GO functions and KEGG pathways. Different subsets of hub genes were obtained based on PPI network. The study then constructed the hub genes-pathway network for different subsets to explore the key signaling pathways and hub genes involved. The findings showed that NRAS and RAC1 functioned through “Rap1 signaling pathway” and “PI3K-Akt signaling pathway”, in male COPD patients. On the other hand, “Cholesterol metabolism” was among the important pathways in female COPD patients while the hub genes, APOE and APOC3 functioned through “Cholesterol metabolism”. Moreover, “Ubiquitin mediated proteolysis” and the “p53 signaling pathway” were shown to play more important roles in male COPD patients compared to their female counterparts. Furthermore, CDK2 and UBE2N were the hub genes involved in “p53 signaling pathway” and “Ubiquitin mediated proteolysis”, respectively. Finally the study identified the relationship between the hub genes and COPD in CTD. Conclusions The present study uncovered different molecular mechanisms in COPD patients based on sex. Additionally, distinct pathways and hub genes including NRAS, RAC1, APOE, APOC3, CDK2 and UBE2N were identified in the two genders of COPD patients. Further studies are needed to explore individualized treatment for COPD based on the findings.

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