In contrast, 8/12 genes (early growth response factor 1, MMP1, MMP9, MMP10, plasminogen activator urokinase, plasminogen activator urokinase receptor, tumor necrosis factor, and IL13) increased and 4/12 (MMP2, tissue inhibitor of matrix metalloproteinase-1, collagen 1alpha1, and transforming growth factor-beta3) decreased in the surrounding lung tissue in association with progression of COPD.
SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD.
In this report, we performed Meta analysis to investigate the association between four kinds of MMP single nucleotide polymorphisms (SNP, MMP1 -1607 1G/2G, MMP3 -1171 5A/6A, MMP9 -1562 C/T, MMP12 -82 A/G) and COPD risk from 21 studies including 4184 cases and 5716 controls.
When stratified by ethnicity, results indicated MMP-1 -1607G/GG (recessive model: G/G vs G/GG+GG/GG; OR: 1.20; 95% CI: 1.01-1.44; p = 0.04) and MMP-9 -1562 C/T (dominant model; OR: 1.66; 95% CI: 1.01-2.71; p = 0.04) were correlated with COPD susceptibility among Caucasians and Asians respectively.
We also found that the chronic obstructive pulmonary disease (COPD)-predisposing TRPV4P19S variant enhances Ca2+ influx and MMP 1 activation, providing mechanistic linkage between man-made air pollution and human airway disease.
Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque.
To investigate the association of 3 polymorphisms of MMP genes (MMP-1 -1607G-->GG, MMP-9 -1562C-->T and MMP-12 N357S), which have been reported to be associated with COPD-related phenotypes, with the risk of COPD in a Korean population.
Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients.
Consequently, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), microsomal epoxide hydrolase (EPHX1), and cytochrome P450 (CYP) genetic polymorphisms may have an important role in COPD pathogenesis.
Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049).
SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease.
In the NETT-NAS case-control analysis, four SFTPD SNPs were associated with susceptibility to COPD: rs2245121 (P = 0.01), rs911887 (P = 0.006), rs6413520 (P = 0.004), and rs721917 (P = 0.006).
Genotype analysis of surfactant protein (SP)-A, SP-B, SP-B-linked microsatellite, and SP-D marker alleles was performed in patients with COPD (n=97) and smoker (n=82) or nonsmoker (n=99) controls.
We compared the genotype frequencies of 12 polymorphisms in seven detoxification-related genes (GSTM1, GSTT1, GSTP1 exon 5, CYP1A1 exon 7, CYP1A1 3'-flanking, CYP2E1 intron 6, CYP2E1 5'-flanking, EPHX1 exon 3, EPHX1 exon 4 and HMOX1 promoter) and the hypoxia-related HIF1A (C1772T and G1790A) genes between 48 Japanese patients with work-related COPD who had a working history in a poison gas factory during World War II and two control groups (n=172 and 110 subjects, respectively).
Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.
The HO-1, NF-κB and 8-OHdG were found highly expressed in COPD rat lung, particularly at the higher PM<sub>2.5</sub> dose of cold stress groups, while Nrf2 was found declined.
Lung protection by heme oxygenase-1 or its enzymatic reaction products has been demonstrated in vitro and in vivo in a number of pulmonary disease models, including acute lung injury, cigarette smoke-induced lung injury/chronic obstructive pulmonary disease, interstitial lung diseases, ischemia/reperfusion injury, and asthma/airway inflammation.