Expression of Epidermal Growth Factors and Their Receptors in the Bronchial Epithelium of Subjects With Chronic Obstructive Pulmonary Disease

Abstract Background Chronic mucus hypersecretion is a common feature in chronic obstructive pulmonary disease (COPD) and is associated with epidermal growth factor (EGF) activity. Aberrant EGF and its receptor signalling can cause airway hyperproliferation, increase in mucous cell differentiation and mucus hyperproduction. Furthermore, it can also promote subepithelial fibrosis and excessive collagen deposition in COPD. The objective of this research was to investigate the plasma levels of EGF in smokers with COPD in comparison with clinically healthy smokers. In addition, the relationship between the plasma levels of EGF and clinical features was investigated. Methods A cross-sectional study included 82 clinically stable male patients with mild-to-very severe COPD (mean age: 64.5±8.6 years), and the control group consisted of 86 healthy male smokers (mean age: 61.6±9.5 years). To define COPD, we performed spirometry and classified COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. We analyzed the levels of EGF by enzyme-linked immunosorbent assay in plasma. Results The mean serum levels of EGF were significantly lower in smokers with COPD than those in controls (69.30 and 83.82 pg/mL, respectively, p = 0.046). The plasma levels of EGF were significantly different (p = 0.004) between mild COPD and moderate-to-very severe COPD. There were no significant differences between the levels of EGF in plasma of spontaneous sputum producers (COPD patients) vs. nonsputum producers (p = 0.101) and between nonexacerbated COPD and exacerbated COPD patients(p = 0.138). Conclusions There is a significant difference in the plasma levels of EGF in male smokers with COPD as compared with male healthy smokers. Our findings suggest that the plasma levels of EGF may contribute to the pathogenesis of COPD.

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Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment

Journal of Cellular Biochemistry ◽

10.1002/jcb.29028 ◽

2019 ◽

Vol 120 (10) ◽

pp. 17602-17615 ◽

Cited By ~ 1

Author(s):

Wen Wen ◽

Guoqing Yu ◽

Wei Liu ◽

Lei Gu ◽

Jiahui Chu ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Cell Apoptosis ◽

Bronchial Epithelium ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Epithelium Cell ◽

Hypoxic Environment

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Platelet-Derived Growth Factors (PDGFs) are Key Players in the Stimulation of Airway Smooth Muscle Cells (ASMCs) Alteration in Asthma and Chronic Obstructive Pulmonary Disease (COPD) with Multifarious Inhibitors at an Early Stage of Development

Current Proteomics ◽

10.2174/1570164617666190906151348 ◽

2020 ◽

Vol 17 (4) ◽

pp. 324-332

Author(s):

Xiaodong Shi ◽

Kwaku Appiah-Kubi

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Smooth Muscle ◽

Growth Factors ◽

Smooth Muscle Cells ◽

Pulmonary Disease ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Chronic Obstructive ◽

Airway Smooth Muscle Cells ◽

Obstructive Pulmonary Disease

Background: Alterations in airway smooth muscle cells cause an increase in their mass and result in a significant impact on airway remodeling diseases such as asthma and chronic obstructive pulmonary disease. Several studies have used platelet-derived growth factors to stimulate the alterations of airway smooth muscle cells. Objective: This review discusses the platelet-derived growth factor-stimulated alterations of airway smooth muscle cells, diversity of inhibitors and inhibitory actions against these alterations and their related mechanisms, and how this diversity presents an avenue for the development of multifarious therapeutic targets for airway remodeling diseases especially asthma and chronic obstructive pulmonary disease. Methods: A comprehensive search of PubMed and Medscape database for studies that investigated the stimulation of the alterations of airway smooth muscle cells in asthma and chronic obstructive pulmonary disease by platelet-derived growth factors and inhibitions of these alterations. Results: Marked platelet-derived growth factor-stimulated alterations of airway smooth muscle cells are proliferation, migration and proliferative phenotype with diverse inhibitors and inhibitory actions against these alterations. Inhibitory actions are the result of the activation of protein kinase, overexpression of Tripartite motif protein, human transporter sub-family ABCA1 protein and miRNAs, knockdown of an isoform of reticulon 4 and follistatin protein, exogenous applications of recombinant proteins, supplements and active metabolite of retinoic acid, flavonoid extracts and polysaccharides extract. Conclusion: The multifarious inhibitors and inhibitory actions with varied mechanisms in platelet-derived growth factors-stimulated alterations of airway smooth muscle cells present a potential for diverse therapeutic targets for the treatment of airway remodeling diseases.

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Expression of GULP1 in bronchial epithelium is associated with the progression of emphysema in chronic obstructive pulmonary disease

Respiratory Medicine ◽

10.1016/j.rmed.2017.02.011 ◽

2017 ◽

Vol 124 ◽

pp. 72-78 ◽

Cited By ~ 1

Author(s):

Sayantan Datta ◽

Hae-Seong Nam ◽

Masamichi Hayashi ◽

Leonel Maldonado ◽

Rachel Goldberg ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Bronchial Epithelium ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

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Oxygen Desaturation Is Associated With Fibrocyte Activation via Epidermal Growth Factor Receptor/ Hypoxia-Inducible Factor-1α Axis in Chronic Obstructive Pulmonary Disease

SSRN Electronic Journal ◽

10.2139/ssrn.3903927 ◽

2021 ◽

Author(s):

Chun-Hua Wang ◽

Chun-Yu Lo ◽

Hung-Yu Huang ◽

Tsai-Yu Wang ◽

Chih-Ming Weng ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Pulmonary Disease ◽

Hypoxia Inducible Factor ◽

Growth Factor Receptor ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Epidermal Growth

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Physiologic and histopathologic effects of targeted lung denervation in an animal model

Journal of Applied Physiology ◽

10.1152/japplphysiol.00565.2018 ◽

2019 ◽

Vol 126 (1) ◽

pp. 67-76 ◽

Cited By ~ 5

Author(s):

James P. Hummel ◽

Martin L. Mayse ◽

Steve Dimmer ◽

Philip J. Johnson

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Primary Source ◽

Experimental Treatment ◽

Bronchial Epithelium ◽

Chronic Obstructive ◽

Clinical Effects ◽

Surface Cooling ◽

Obstructive Pulmonary Disease ◽

Long Acting

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.

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