Transforming growth factor-beta1 is a potent mediator of fibrosis stimulating the secretion of extracellular matrix proteins and is involved in airway remodeling in chronic obstructive pulmonary disease (COPD).
Transforming growth factor-β(1) (TGF-β(1)) is upregulated in asthma and COPD and contributes to tissue remodeling in the airways by driving ECM production by structural cells, including airway smooth muscle.
Abnormal expression of TGF-beta1 is believed to play an important role in the pathogenesis of a number of chronic inflammatory and immune lung diseases, including asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.
After carbachol (CCh) or transforming growth factor-β1 (TGF-β1) exposure, the response to glycopyrronium and indacaterol was determined in vitro in fibroblasts isolated from mild-to-moderate COPD lung tissue.
Eight SNPs in TGFB1 (rs2241712, rs1982072, and rs1800469 in the promoter region; rs1982073 in exon 1; rs2241716 and rs4803455 in intron 2; rs6957 and rs2241718 in the 3' region) were genotyped by allelic discrimination assays in 70 COPD patients with emphysema phenotype and 99 healthy smokers.
Furthermore, compared with untreated rats with COPD, <i>C. sinensis</i> reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD.
Haplotype analysis showed that the frequencies of the GC, GT haplotypes of rs2241718 (TGF-β1 gene), and rs6957 (CDC97 gene) were significantly higher in the control group than in the COPD case group (p=1.88×10-9); the frequencies of the TT haplotype of rs1205 and rs2808630 (CRP gene) were significantly higher in the control group (p=0.0377).
Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms.
In addition, increased expression of TGF-beta1 in COPD lungs and primary cells, such as epithelial cells, macrophages, or fibroblasts isolated from COPD specimens, was reported, suggesting an impact of TGF-beta signalling on the development and progression of COPD.
It has been hypothesized that polymorphisms in the transforming growth factor-β1 (<i>TGF-β1</i>) gene on chromosome 19 modify the risk for chronic obstructive pulmonary disease (COPD).
LPS directly induced CTGF expression in bronchial epithelial cells, independently of transforming growth factor-beta1, suggesting a possible mechanism for airway remodelling in COPD that is induced by smoking and repeated bacterial infections.
Moreover, as a combination of tumor necrosis factor-α (TNF-α) and TGF-β1 have been shown to have a cumulative impact on the severity of airflow limitation in COPD, the TNF-α release was also measured in a representative subgroup of patients.
Of these variants, four were significantly associated with COPD susceptibility in random effects meta-analysis, the GSTM1 null variant (OR 1.45, CI 1.09-1.92), rs1800470 in TGFB1 (0.73, CI 0.64-0.83), rs1800629 in TNF (OR 1.19, CI 1.01-1.40) and rs1799896 in SOD3 (OR 1.97, CI 1.24-3.13).
Polymorphisms of promoters of TNF-α (rs 361525 and rs 1800629) and TGF-β1 (rs 1800469) in 110 COPD patients, 110 nonsmoker health controls without COPD, and 34 smokers were evaluated.
Published human microarray and murine linkage studies have also demonstrated the importance of TGFBR3 in emphysema and lung function, and our group and others have previously found association of COPD-related traits with TGFB1, a ligand for TGFBR3.
SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD.
Spontaneously released immunoreactive TGF-beta1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers.
Taken together, we propose that TGFβ1 is responsible for the generation of CD4<sup>+</sup>CD25<sup>-</sup>Foxp3<sup>+</sup> T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD.
The 2.5 kb TGF-beta 1 mRNA was seen in all 18 samples analysed by Northern blotting and densitometric analysis showed no difference between the asthmatic group (mean (SD) 108% (43%)), the group with COPD (122% (33%)), and the non-obstructed group (100% (49%)).