High expression of high‐mobility group box 1 in the blood and lungs is associated with the development of chronic obstructive pulmonary disease in smokers

Ko, Hsin Kuo; Hsu, Wen Hu; Hsieh, Chih Cheng; Lien, Te Cheng; Lee, Tzong‐Shyuan; Kou, Yu Ru

doi:10.1111/resp.12209

Cited by 24 publications

(27 citation statements)

References 33 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma HMGB1, along with sRAGE, has been found to be higher during acute exacerbations in COPD patients and lower during convalescence46. Increased HMGB1 has been observed in blood and lung of smokers with COPD relative to healthy smokers47. There is also evidence of elevated HMGB1 protein levels in the sputum48 and bronchoalveolar lavage (BAL)37 of COPD patients.…”

Section: Discussionmentioning

confidence: 99%

Functional interactors of three genome-wide association study genes are differentially expressed in severe chronic obstructive pulmonary disease lung tissue

Morrow

Zhou

Lao

et al. 2017

Sci Rep

118

View full text Add to dashboard Cite

In comparison to genome-wide association studies (GWAS), there has been poor replication of gene expression studies in chronic obstructive pulmonary disease (COPD). We performed microarray gene expression profiling on a large sample of resected lung tissues from subjects with severe COPD. Comparing 111 COPD cases and 40 control smokers, 204 genes were differentially expressed; none were at significant GWAS loci. The top differentially expressed gene was HMGB1, which interacts with AGER, a known COPD GWAS gene. Differentially expressed genes showed enrichment for putative interactors of the first three identified COPD GWAS genes IREB2, HHIP, and FAM13A, based on gene sets derived from protein and RNA binding studies, RNA-interference, a murine smoking model, and expression quantitative trait locus analyses. The gene module most highly associated for COPD in Weighted Gene Co-Expression Network Analysis (WGCNA) was enriched for B cell pathways, and shared seventeen genes with a mouse smoking model and twenty genes with previous emphysema studies. As in other common diseases, genes at COPD GWAS loci were not differentially expressed; however, using a combination of network methods, experimental studies and careful phenotype definition, we found differential expression of putative interactors of these genes, and we replicated previous human and mouse microarray results.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional interactors of three genome-wide association study genes are differentially expressed in severe chronic obstructive pulmonary disease lung tissue

Morrow

Zhou

Lao

et al. 2017

Sci Rep

118

View full text Add to dashboard Cite

show abstract

“…In their study, the serum HMGB1 levels were higher in COPD patients with more severe airflow limitation (mean %FEV 1 , 49%) when compared with the results in the present study, and they found that patients with lung cancer had even higher levels of serum HMGB1. In another recent study that has reported elevated plasma HMGB1 levels in patients with mild to moderate COPD, 82% of the COPD patients had comorbid lung cancer [15]. In fact, our study is the first to compare circulatory HMGB1 levels between never-smokers, a control group of smokers without COPD, and smokers with early stage COPD and no comorbidities, and the inconsistencies of the HMGB1 levels in the COPD patients in the present study and those of the previous studies are probably related to the differences in the background characteristics of the study participants.…”

Section: Discussionmentioning

confidence: 99%

“…It has recently been shown that HMGB1 is up-regulated in COPD lung tissue and co-localised with RAGE [12]. Furthermore, circulatory HMGB1 levels are elevated in patients with COPD, especially in those with more severe airflow limitation or in cases complicated by comorbid lung cancer [13-15]. …”

Section: Introductionmentioning

confidence: 99%

Soluble receptor for advanced glycation end-products and progression of airway disease

et al. 2014

View full text Add to dashboard Cite

BackgroundThe receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role. Reduced plasma levels of soluble RAGE (sRAGE) have been reported in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the association of plasma sRAGE levels with a longitudinal decline of lung function. We have also measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD.MethodsBaseline plasma concentrations of sRAGE and HMGB1 were measured in non-smokers (n = 32), smokers without COPD (n = 212), and smokers with COPD (n = 51), and the associations of the plasma sRAGE and HMGB1 levels with longitudinal declines of lung function during a 4-year follow-up period were analysed.ResultsThe plasma levels of sRAGE were significantly lower in smokers without COPD and in smokers with COPD, as compared to those of non-smokers. Plasma sRAGE levels positively correlated with FVC and FEV1 and inversely correlated with BMI and pack-years. Lower sRAGE levels were associated with greater declines of FEV1/FVC over 4 years in all participants. Moreover, multivariate regression analysis indicated that the baseline plasma sRAGE concentration was an independent predictor of FEV1/FVC decline in all groups. A subgroup analysis showed that decreased sRAGE levels are significantly associated with a more rapid decline of FEV1/FVC in smokers with COPD. There was no significant correlation between plasma HMGB1 levels and longitudinal decline of lung function.ConclusionsLower plasma concentrations of sRAGE were associated with greater progression of airflow limitations over time, especially in smokers with COPD, suggesting that RAGE might have a protective role in the lung.

show abstract

“…Macrophages, neutrophils, and T lymphocytes can release cytokines, including IL-1β and HMGB1, which are responsible for sustaining inflammation and remodeling during COPD. Serum or sputum HMGB1 as well as other RAGE ligands are increased in COPD patients, suggesting that the RAGE pathway is critical in the pathophysiology of COPD (Ferhani et al, 2010; Hou et al, 2011a; Kanazawa et al, 2012; Ko et al, 2013; Pouwels et al, 2014; Sukkar et al, 2012). …”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

798

828

View full text Add to dashboard Cite

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

show abstract

High expression of high‐mobility group box 1 in the blood and lungs is associated with the development of chronic obstructive pulmonary disease in smokers

Abstract: In smokers, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD.

Cited by 24 publications

References 33 publications

Functional interactors of three genome-wide association study genes are differentially expressed in severe chronic obstructive pulmonary disease lung tissue

Functional interactors of three genome-wide association study genes are differentially expressed in severe chronic obstructive pulmonary disease lung tissue

Soluble receptor for advanced glycation end-products and progression of airway disease

HMGB1 in health and disease

Contact Info

Product

Resources

About