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.
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.
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.
The level of MMP-9 was significantly higher in COPD patients with >3 comorbidities, a COTE index of ≥4 and cardiovascular disease as well as coronary heart disease (t=6.40, 2.53, 3.65 and 2.90, P<0.05).
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.
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.
Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD..
Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD.