Role of the HIF-1 signaling pathway in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is the most common cause of chronic morbidity and mortality. However, the molecular mechanisms underlying COPD remain largely unknown. The purpose of the present study was to investigate the expression patterns of hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and VEGF receptor 2 (R2) in regard to the HIF-1 signaling pathway in COPD. The expressions of HIF-1α, VEGF and VEGFR2 were examined and quantified in the human lung tissues of 102 subjects with a defined smoking status, with or without COPD. The expressions of HIF-1α, VEGF and VEGFR2 were observed to be increased in the lung tissues collected from smoking COPD subjects when compared with those tissues from smoking subjects without COPD and non-smoking subjects without COPD. The expression of HIF-1α was shown to be positively associated with the expression of VEGF and VEGFR2. In addition, increased expression of HIF-1α, VEGF and VEGFR2 reflected the disease severity of COPD. The key findings obtained from the present study indicated that high expression of HIF-1α, VEGF and VEGFR2 may be associated with decreased lung function and reduced quality of life, contributing to disease progression in COPD.

Keywords: chronic obstructive pulmonary disease; hypoxia inducible factor-1α; hypoxia-inducible factor 1α signaling pathway; vascular endothelial growth factor; vascular endothelial growth factor receptor.

Figure 1.

Smoking COPD subjects exhibited (A) reduced quality of life (reflected by CAT scores) and (B) an increased degree of dyspnea (reflected by mMRC grades). P<0.001, as indicated. COPD, chronic obstructive pulmonary disease; mMRC, Modified Medical Research Council scale; CAT, COPD Assessment Test.

Figure 2.

Morphological alterations of the lung tissue, detected by hematoxylin and eosin staining. (A) Lung tissue of non-smoking without COPD group (magnification, ×100); (B) lung tissue of smoking without COPD group (magnification, ×100); (C) lung tissue of smoking COPD group (magnification, ×100); (D) airway tissue of non-smoking without COPD group (magnification, ×400); (E) airway tissue of smoking without COPD group (magnification, ×400); and (F) airway tissue of smoking COPD group (magnification, ×400). COPD, chronic obstructive pulmonary disease.

Figure 3.

Expression of (A) hypoxia inducible factor-1α, (B) VEGF and (C) VEGF receptor 2 was observed to be increased in the lung epithelium collected from smoking chronic obstructive pulmonary disease subjects, as detected by immunohistochemistry (magnification, ×200 and ×400 as indicated). VEGF, vascular endothelial growth factor.