Proteomic studies on receptor for advanced glycation end product variants in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease

Ohlmeier, Steffen; Mazur, Witold; Salmenkivi, Kaisa; Myllärniemi, Marjukka; Bergmann, Ulrich; Kinnula, Vuokko L.

doi:10.1002/prca.200900128

Cited by 47 publications

(51 citation statements)

References 33 publications

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“…For Western blotting, equal volumes of the sputum supernatants (n ϭ 14/group) were loaded. Ponceau S staining was used to standardize the loading of the sputum and lung homogenates (25) to avoid problems with the conventional loading markers in COPD (10,13,29). The samples were run as two sets of samples on the gels: nonsmokers (n ϭ 7) vs. smokers (n ϭ 7) and nonsmokers (n ϭ 7) vs. COPD (n ϭ 7).…”

Section: Methodsmentioning

confidence: 99%

“…In recent proteomic studies from our laboratory the major findings included an elevation of surfactant protein-A (SP-A) and a decrease of specific variants of the receptor for advanced glycation end products (RAGE) in lung tissue (25,26) and polymeric immunoglobulin receptor in sputum samples from patients with COPD (24). Of these, SP-A and soluble RAGE have been validated in longitudinal approaches in larger cohorts (16,20).…”

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confidence: 99%

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Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing foldcontaining protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n ϭ 31), smokers (n ϭ 169), and patients with COPD (n ϭ 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV 1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smokingrelated lung diseases.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor abundantly expressed in type I pneumocytes. The expression of RAGE is significantly decreased in COPD lung, especially in severe disease [12]. The soluble isoform of RAGE (sRAGE) in plasma might represent a potential marker of COPD, as its levels decline in patients with COPD and decrease further during exacerbations [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

et al. 2013

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The pathophysiological features of chronic obstructive pulmonary disease (COPD)-asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells.Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n526), smokers (n523), asthma (n532), COPD (n539) and COPD-asthma overlap patients (n514).In patients with COPD-asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD-asthma overlap compared with COPD (p50.00016) and could be used to differentiate patients with overlap from those with COPD.Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap. @ERSpublications Increased sputum levels of neutrophil gelatinase-associated lipocalin in COPD-asthma overlap versus COPD/asthma patients

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“…High RAGE expression prior to the alveolarization period has adverse effects associated with a severe pulmonary dysplasia (16,41). A reduced alveolar expression of RAGE is related to pathophysiological changes of the lung tissue, such as carcinoma (3), fibrosis (34,37), and chronic obstructive pulmonary disease (COPD) (34). In addition to the membrane-bound receptor, soluble RAGE (sRAGE) forms exist as the result of either alternative splicing (22) or protein shedding by metalloproteinases (39,52).…”

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confidence: 99%

The receptor for advanced glycation end-products supports lung tissue biomechanics

Al‐Robaiy

Weber

Simm

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-␣, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.receptor for advanced glycation end-products; aging; biomechanics; elastin; mouse THE RECEPTOR FOR ADVANCED glycation end-products (RAGE) is a pattern recognition receptor of the immunoglobulin superfamily (32). RAGE is predominantly expressed in lung, particularly in the type I alveolar epithelial (ATI) cells (12,15,46). This specific localization suggests its important physiological function in the alveolar epithelium. In other cell types and tissues, the expression of RAGE is activated in response to pathophysiological conditions, such as the accumulation of advanced glycation end-products (AGEs) and inflammation (1). RAGE expression is highly associated with lung development and increases during the alveolarization (29,40). High RAGE expression prior to the alveolarization period has adverse effects associated with a severe pulmonary dysplasia (16,41). A reduced alveolar expression of RAGE is related to pathophysiological changes of the lung tissue, such as carcinoma (3), fibrosis (34, 37), and chronic obstructive pulmonary disease (COPD) (34). In addition to the membrane-bound receptor, soluble RAGE (sRAGE) forms exist as the result of either alternative splicing (22) or protein shedding by metalloproteinases (39, 52). sRAGE normally exists in the bronchoalveolar lavage (BAL) at a high level (53), but it is deficient in neutrophilic asthma and COPD (47, 49).The physiological importance of RAGE in lung is not yet fully understood because mice lacking RAGE do not show obvious pulmonary alterations (5, 9). Only intervention studies indicated an adverse effect of RAGE in the development of lung fibrosis (14, 19) and acute lung injury (4...

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Proteomic studies on receptor for advanced glycation end product variants in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease

Abstract: This study shows an involvement of the three RAGE variants (FL-RAGE, cRAGE, esRAGE) in IPF. The decline of FL-RAGE and cRAGE, but not esRAGE, in COPD lungs is evidence of involvement of specific RAGE variants also in this disease.

Cited by 47 publications

References 33 publications

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

The receptor for advanced glycation end-products supports lung tissue biomechanics

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