MMP-9 (gelatinase B) is recognized in chronic obstructive pulmonary disease (COPD) and now asthma as playing a central role in matrix degradation in injury, as well as contributing to the remodeling process.
Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive Pulmonary Disease.
According to source of controls, significant association of MMP-9-1562 C/T (additive model: T vs C; OR:1.71, 95% CI: 1.42-2.07; p<0.00001, and dominant model; OR: 1.92; 95% CI: 1.34-2.76; p = 0.0004) with COPD susceptibility was revealed in the subgroup with smoker-based controls.
Additionally, specific activation of phosphoinositide 3‑kinase (PI3K) signaling, using insulin‑like growth factor‑1 (IGF‑1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF‑1, PI3K, AKT, phospho‑AKT, serine/threonine‑protein kinase mTOR (mTOR), phospho‑mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP‑9 in cells from COPD rats.
Additionally, the significant inverse relationships between parameters of lung function (FEV<sub>1</sub>% and FEV<sub>1</sub>/FVC) and proteins level were found in ridge regression models, especially we found that FEV<sub>1</sub>% decreased when MMP-9 level increased in controls and patients with COPD group.
As the major clinical characteristics of stage 4 COPD is the development of pulmonary emphysema as well as bronchial walls deformation, we suggest that the increased expression of MMP9 gene caused by genetic polymorphism in the gene promoter is important in the early development of serious complications of the disease.
Based on our meta-analysis, MMP-9rs3918242 C > T is correlated with susceptibility to COPD, but MMP-1 rs1799750 1G > 2G and MMP-3 rs3025058 5A > 6A are not.
Baseline plasma concentration of anti-elastin antibodies and elastin-degrading enzymes (eg, matrix metalloproteinase-9, and -12, and neutrophil elastase) were measured in the same cohort. elastin fragment-specific CD 4<sup>+</sup> T cell expression of interferon-γ, and anti-elastin antibodies were dependent on history of smoking in TAA / TAD patients but were independent of chronic obstructive pulmonary disease.
By anchoring MMP-8 and MMP-9 to PMN surfaces, membrane-bound TIMP-1 plays a counterintuitive role in promoting PMN pericellular proteolysis occurring in chronic obstructive pulmonary disease and other diseases.
Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and was also associated with increased skin elastin degradation (r=0.62, p<0.001 and r=0.47, p=0.01, respectively).
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.
However, concentration ratio of MMP-9 released from PMN exposed to 4% CSE or 0% CSE of each participant was significantly higher for healthy subjects than for COPD patients (P = 0.025).
However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients.
In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00-2.90; and OR, 3.03; 95%CI, 1.02-9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23-1.7; and IRR, 1.24; 95%CI, 1.03-1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively.
In conclusion, this study shows that MMP-9 expression in human lung parenchyma is associated with cigarette smoking and also with the obstruction of airflow, suggesting that MMP-9 may play a role in the pathogenesis of the cigarette smoke-induced obstruction of airflow known as the characteristic of COPD.
Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).