Altered expression of the Smad signalling pathway: implications for COPD pathogenesis

Zandvoort, Andre; Postma, Dirkje S.; Jonker, Marnix; Noordhoek, Jacobien A.; Vos, Jaap Jan; Geld, Ymke M. van der; Timens, Wim

doi:10.1183/09031936.06.00078405

Cited by 72 publications

(63 citation statements)

References 27 publications

(42 reference statements)

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“…Loss of decorin in the lung may contribute to loosening of the collagen fibre network and higher levels of active transforming growth factor-b. As we have shown that decorin is consistently reduced in its presence and production in COPD [33,34,43], it will be of interest to evaluate whether a humoral autoimmune response may be involved. The next step is to also perform ELISPOT analysis on lung tissue to find out whether these anti-decorin IgG antibody-producing cells are also prominent in the lungs of COPD patients.…”

Section: Discussionmentioning

confidence: 99%

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Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

et al. 2012

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Several studies have demonstrated the presence of B-cell follicles and autoantibodies in chronic obstructive pulmonary disease (COPD). It is unclear against which antigens this B-cell response is directed and whether it contributes to development or worsening of disease.We assessed different B-cell subsets in blood and lung tissue from COPD patients and controls, and compared differences in B-cell responsiveness to stimulation with lung-specific antigens.Active smoking induced an adaptive immune response with relatively high levels of (classswitched) memory B-cells in blood and immunoglobulin (Ig)G memory B-cells in the lung. COPD smokers showed more switching to IgG, whereas healthy smokers switched more to IgA. COPD patients had higher levels of memory B-cells in the lung and stimulation with lung-specific antigens induced higher numbers of anti-decorin antibody-producing cells in COPD patients compared with healthy controls.Differential switching to IgG and IgA indicates that the adaptive immune response to smoke differs between COPD patients and healthy controls. A higher level of memory B-cells in the lungs of COPD patients may reflect an antigen-specific immune response, which could be directed against decorin, as suggested by the induction of anti-decorin antibody-producing cells in response to antigen-specific stimulation in COPD patients.

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Section: Discussionmentioning

confidence: 99%

“…Given the previous results of LEE et al [14], our own recent data regarding autoantibodies against elastin, collagen and decorin [21,32], and our previous findings regarding a decreased presence of decorin in COPD [33,34], we chose elastin, collagen and decorin as lung-specific antigens in this study.…”

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confidence: 99%

Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

et al. 2012

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“…Decreased expression of TGF-b1, TbRI, and Smad3 has been reported in lung tissue specimens from patients with stage II COPD compared with normal control subjects (60). Moreover, cultured pulmonary fibroblasts from patients with emphysema show reduced response to TGF-b1 stimulation accompanied by increased levels of inhibitory Smad7 (Smad2/3 inhibitor) and reduced Smad3 activation, although TGF-b ligand production is increased (61).…”

Section: Abnormalities In Genes Involved In Tgf-b-smad Signaling Are mentioning

confidence: 99%

Mechanisms of Lung Development: Contribution to Adult Lung Disease and Relevance to Chronic Obstructive Pulmonary Disease

Shi¹,

Chen²,

Cardoso³

2009

Proceedings of the American Thoracic Society

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“…The main pathological change of emphysema is the destruction of extracellular matrix (ECM) components around the alveoli (Zandvoort et al 2006). It is associated with the imbalance of proteinase and antiproteinase activity which progressive proteolytic destruction without adequate repair.…”

mentioning

confidence: 99%

“…Tissue inhibitor of metalloproteinase (TIMP-1) is an important anti-protease of MMP-2 and MMP-9 in the lung. Another key modulating factor, transforming growth factor-β (TGF-β ), also affects the expression of ECM components (McGowan et al 1997;Morris et al 2003;Zandvoort et al 2006).…”

mentioning

confidence: 99%

Disruption of Plasminogen Activator Inhibitor-1 Gene Enhances Spontaneous Enlargement of Mouse Airspace with Increasing Age

Zhao

Xiao

et al. 2010

Tohoku J. Exp. Med.

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Plasminogen activator inhibitor-1 (PAI-1) is the most effective protease inhibitor in the fibrinolysis system, and plays an important role in the remodeling of the extracellular matrix. We therefore explored whether PAI-1 is involved in the change of lung structure with increasing age. PAI-1 gene knockout mice and wild-type mice were sacrificed at age 3 weeks, 3 months, 6 months and 15 months for histopathology analysis, and assessed the relationship between PAI-1 and the change in lung structure with age. Six-month-old mice were chosen for further studies. Elastin in the lung was detected using Weigert staining. We measured the expression of matrix metalloproteinase-12 (MMP-12) that is a major protease in elastin degradation by real time PCR and immunostaining. Transforming growth factor-β 1 (TGF-β 1) expression was measured by western blot analysis. PAI-1 gene knockout mice showed significant increases in alveolar size with increasing age and damaged alveolar structure at the age of 15 months, compared with wild-type mice. At the age of 6 months, elastin protein was decreased in the lungs of PAI-1 gene knockout mice. PAI-1 null mice had higher MMP-12 mRNA expression, and lower expression level of active TGF-β 1 in the lung. Taken together, these results indicate that the emphysema-like change attributed to PAI-1 deficiency might be facilitated with increased MMP-12 expression that accelerates elastin degradation in mice lungs, and TGF-β 1 might be involved in the modulation of this process.

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Altered expression of the Smad signalling pathway: implications for COPD pathogenesis

Cited by 72 publications

References 27 publications

Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

Mechanisms of Lung Development: Contribution to Adult Lung Disease and Relevance to Chronic Obstructive Pulmonary Disease

Disruption of Plasminogen Activator Inhibitor-1 Gene Enhances Spontaneous Enlargement of Mouse Airspace with Increasing Age

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