Figure 2 - uploaded by Alvar Agusti
Content may be subject to copyright.
HGF concentration in serum in the three groups of individuals studied. Abbreviation: HGF, hepatocyte growth factor.
Source publication
The potential role of growth factors in chronic obstructive pulmonary disease (COPD) has begun to be addressed only recently and is still poorly understood. For this study, we investigated potential abnormalities of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in patients with COPD.
To this end, we compared the levels of HGF...
Contexts in source publication
Context 1
... 19 mg/ml (9-38 mg/ml); and, never smokers 11 mg/ml (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In contrast, the serum concentra- tion of HGF was higher (p 0.01) in smokers with normal lung function (1897 pg/ml ) than in patients with COPD (1053 pg/ml ) and never smokers (700 pg/ml ) (Figure 2). ...
Context 2
... ( between the degree of airfl ow obstruction and HGF mRNA in lung tissue of smokers with and without COPD, which seem to agree with the results of our study (Figure 1). Interest- ingly, other growth factors, such as fi broblast growth factor (FGF) −1 and −2 appear also to be increased in bronchial airway wall ( Kranenburg et al 2005) and placental growth factor in BAL in patients with COPD (Cheng et al 2008). Therefore, the results of our study in combination with other previous ones ( , where a similar HGF response has been described. ...
Context 3
... latter observation fully agrees with our results, albeit we extend their observations to include smokers with normal lung function (Table 1). Like Palange and colleagues (2006) we found that HGF serum levels were higher in COPD patients than in never smokers, but this increase was much enhanced in smokers with normal lung function (Figure 2). This may suggest a blunted systemic response that may potentially limit lung repair. ...
Context 4
... methodological aspects of our study deserve comment. First, because it is known that smoking increases HGF (Chen et al 2006), we confi rmed that participants refrained from smoking 12 hours before bronchoscopy by measuring the exhaled CO concentration (which was lower than 10 ppm in all participants). Second, albeit patients with COPD had higher smoking exposure that smokers with normal lung func- tion we do not believe that this infl uenced our results because we did not fi nd any correlation between smoking exposure (pack-yrs) and levels of growth factors. ...
Context 5
... in patients with lung cancer, an overexpression of HGF in lung tissue close to the tumor has been reported (Chen et al 2006). Yet, we think that this did not biased our results because we studied patients with Stage I lung cancer in whom the over expression of HGF is negligible ( Chen et al 2006), BAL was always performed in the lung without chest X-ray anomalies and HGF levels were not different in smokers with and without cancer. Fourth, although steroids can modulate the concentration of growth factors (Blanquaert et al 2000), results were unchanged after excluding the 4 patients treated with ICS. ...
Similar publications
Jaume Sauleda1, Aina Noguera2, David Blanquer3, Jaume Pons4, Meritxell López1, et al1Servei de Pneumologia, Hospital Universitari Son Dureta, Fundació Caubet-Cimera Illes Balears, Illes Balears, CIBER Enfermedades respiratorias, Illes Balears, Spain; 2Inmunologia, 4Anàlisis Clínique, Hospital Universitari Son Dureta. Palma Mallorca, Spain; 3Fundaci...
Citations
... On the other hand, hepatocyte growth factor was increased in saliva of smokers with periodontitis [51]. Similarly, smokers suffering from COPD showed higher levels of hepatocyte growth factor in bronchial lavage [52]. Therefore, INSR and related hepatocytes and/or hepatocyte growth factors might be a shared genetic and immunological marker, especially in smokers affected by periodontitis and COPD. ...
Background
The aim of this study was to detect potential crosstalk genes, pathways and immune cells between periodontitis and chronic obstructive pulmonary disease (COPD).
Methods
Chronic periodontitis (CP, GSE156993) and COPD (GSE42057, GSE94916) datasets were downloaded. Differential expressed genes (DEGs; p < 0.05) were assessed and screened for overlapping results, following functional pathway enrichment analyses (p < 0.05). The xCell method was used to assess immune cell infiltration relationship between CP and COPD. Features of the detected cross-talk genes were revealed using conventional Recursive Feature Elimination (RFE) algorithm in R project. Receiver-operating characteristic curves were applied to evaluate the predictive value of the genes. Furthermore, Pearson correlation analysis was performed on crosstalk markers and infiltrating immune cells in CP and COPD, respectively.
Results
A total of 904 DEGs of COPD and 763 DEGs of CP were acquired, showing 22 overlapping DEGs between the two diseases. Thereby 825 nodes and 923 edges were found in the related protein–protein-interaction network. Eight immune cell pairs were found to be highly correlated to both CP and COPD (|correlation coefficients |> 0.5 and p-value < 0.05). Most immune cells were differently expressed between COPD and CP. RFE identified three crosstalk genes, i.e. EPB41L4A-AS1, INSR and R3HDM1. In correlation analysis, INSR was positively correlated with Hepatocytes in CP (r = 0.6714, p = 0.01679) and COPD (r = 0.5209, p < 0.001). R3HDM was positively correlated with Th1 cells in CP (r = 0.6783, p = 0.0153) and COPD (r = 0.4120, p < 0.01).
Conclusion
EPB41L4A-AS1, INSR and R3HDM1 are potential crosstalk genes between COPD and periodontitis. R3HDM was positively correlated with Th1 cells in both diseases, while INSR was positively correlated with Hepatocytes in periodontitis and COPD, supporting a potential pathophysiological relationship between periodontitis and COPD.
... Hepatocyte growth factor was involved in the pathogenesis of various lung diseases as it was significantly higher in COPD patients compared to control patients. Hence, the "cellular response to hepatocyte growth factor stimulus" might be relevant for tissue repair in COPD [36]. The remodeling of the "extracellular matrix organization" is a common feature in lung diseases such as COPD [37]. ...
Background
Identifying or prioritizing genes for chronic obstructive pulmonary disease (COPD), one type of complex disease, is particularly important for its prevention and treatment.
Methods
In this paper, a novel method was proposed to Prioritize genes using Expression information in Protein–protein interaction networks with disease risks transferred between genes (abbreviated as PEP). A weighted COPD PPI network was constructed using expression information and then COPD candidate genes were prioritized based on their corresponding disease risk scores in descending order.
Results
Further analysis demonstrated that the PEP method was robust in prioritizing disease candidate genes, and superior to other existing prioritization methods exploiting either topological or functional information. Top-ranked COPD candidate genes and their significantly enriched functions were verified to be related to COPD. The top 200 candidate genes might be potential disease genes in the diagnosis and treatment of COPD.
Conclusions
The proposed method could provide new insights to the research of prioritizing candidate genes of COPD or other complex diseases with expression information from sequencing or microarray data.
... KGF, encoded by the FGF7 gene, is mainly related to the repair of the lung, and that is mostly due to their capacity to stimulate alveolar and bronchial epithelial cell proliferation [15,16]. Although the potential role of FGF7 in influencing the risk of COPD is poorly understood, functional studies have been performed to investigate gene expression abnormalities of the FGF7 in patients with COPD [17]. A study showed that the KGF levels were not notably different between patients with COPD and healthy controls in bronchoalveolar lavage (BAL) fluid or in serum, which may be due to the limitation of the KGF detection method used in the samples [17]. ...
... Although the potential role of FGF7 in influencing the risk of COPD is poorly understood, functional studies have been performed to investigate gene expression abnormalities of the FGF7 in patients with COPD [17]. A study showed that the KGF levels were not notably different between patients with COPD and healthy controls in bronchoalveolar lavage (BAL) fluid or in serum, which may be due to the limitation of the KGF detection method used in the samples [17]. Also, studies on the role of human recombinant KGF in modulating lung function have also been conducted in cell-based assays and mouse models. ...
Background
Genome-wide association studies (GWASs) of a large cohort of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified multiple risk genes, including fibroblast growth factor 7 (FGF7). However, the underlying molecular mechanism influencing function of FGF7 and risk of COPD remains further study.
Methods
In this study, we replicated the genetic association of variants near the FGF7 gene in 258 Chinese Han patients with COPD and 311 healthy controls. Additionally, we functionally evaluated a candidate causal variant upstream of the FGF7 gene.
Results
The most significant association was observed at rs12905203 (P = 5.9 × 10− 3, odd ratio, OR = 1.516) that explains associations of previously reported variants at the FGF7 locus. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays showed that the risk allele of the variant was bound to activator protein 1 transcription factors (c-Fos and c-Jun) with a significantly reduced affinity and associated with decreased mRNA expression of FGF7 in fibroblast cells at both resting and PMA/Ionomycin-stimulated conditions. Overexpression of c-Fos and c-Jun proteins or stimulation with PMA/Ionomycin significantly increases mRNA expression of FGF7 in fibroblast cells. Bioinformatic analysis showed that the variant overlaps with multiple genetic regulatory marks, suggesting the regulatory DNA element might function as an enhancer for the FGF7 gene. Luciferase enhancer activity assays demonstrated that the DNA sequences carrying the variant produce enhancer activity while the risk allele of the variant reduces its activity.
Conclusions
In this study, we demonstrated a consistent association of the FGF7 gene with COPD and mechanistically characterized a candidate functional variant upstream of the FGF7 gene. These data highlighted the important role of the risk variant and the FGF7 gene in influencing risk for COPD.
Electronic supplementary material
The online version of this article (10.1186/s12881-019-0761-7) contains supplementary material, which is available to authorized users.
... However, the correlation between c-Met and HGF expression did not reach statistical significance. This may be explained by the fact that HGF is secreted by carcinoma cells as well as CAFs [32] and in other inflammatory processes, including alcoholic hepatitis, cirrhosis, smoking, and chronic obstructive pulmonary disease [36,37]. We therefore analyzed the correlation between c-Met/HGF immunoreactivity and preoperative levels of %VC, FEV 1.0 %, CRP, ICG-R15, AST, and ALT owing to the high frequency of alcohol consumption and smoking history in ESCC patients, but found no significant correlation. ...
BACKGROUND: c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients.
METHODS: The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines.
RESULTS: Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor.
CONCLUSIONS: The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.
... Consistent with other studies [42,43], there was evidence that they correlated with GOLD stage and amount of emphysema and so may be useful in differentiating individuals with emphysema from those with predominantly airway disease. Hepatocyte growth factor plays a role in tissue regeneration [44] and was shown in a small study to be increased in bronchoalveolar lavage of COPD subjects and smokers with normal lung function [45]. The repeatability of MMP-8 remains untested; however the wide variability of MMP-9 and hepatocyte growth factor over 3 months suggests that they are unlikely to be useful in clinical applications. ...
There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.
Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.
Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.
Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.
SCO104960, clinicaltrials.gov identifier NCT00292552.
The complex disorders of chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia (BPD) are common, costly, and clinically burdensome. Both lung disorders develop after complex injurious triggers and can result in significant lung disease and disability. Similarities in their lung pathology and injury measures suggest common pathogenetic mechanisms. Evidence exists for both common molecular triggers and for injury-by-age interactions that may confer distinct end pathology. An emerging concept is that BPD may be a predisposing pathology for COPD development in late life. Future studies focusing on this provocative connection between BPD and COPD may translate into novel ameliorative and regenerative therapies for both disorders.
