The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.

Xianyan Liu,Xiaoming Liu,Jinxi He,Juan Chen,Ailing Ma,Binwei Hao

doi:10.1155/2016/2891810

Abstract

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-β signaling in the pathogenesis of COPD, which warrants further investigation.

Highlights

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases characterized by persistent airflow limitation, along with the presence of both oxidative stress and airway inflammation [1, 2]
The selected criteria of the values of pulmonary function, FEV1% pred, FEV1, forced vital capacity (FVC), and FEV1/FVC%, were significantly different in patients with COPD compared to the patients without COPD (p = 0.003 for FVC, and p = 0.000 for FEV1% pred, FEV1, and FEV1/FVC%) (Table 1)
The activated transforming growth factor β (TGF-β)/reactive oxygen species (ROS) signaling promotes airway smooth muscle (ASM) remodeling by facilitating muscle cell proliferation and fibroblast myofibrosis and enhanced extracellular matrix (ECM) synthesis and deposition [37, 47]. Consistent with this notion, our results revealed that the expression of NOX4 and TGF-β was elevated in the epithelial cells and ASM cells of small airways of COPD lung, and the NOX4 level was tightly correlated with the TGF-β expression in ASM

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases characterized by persistent airflow limitation, along with the presence of both oxidative stress and airway inflammation [1, 2]. In China, the overall prevalence of COPD was 8.2% as defined by the criteria of Global Initiative for Obstructive Lung Disease [3,4,5]. Mechanisms involving chronic airway inflammation, oxidant and antioxidant imbalance caused by overwhelming oxidative stress, protease and antiprotease imbalance, cell apoptosis, and airway remodeling have recently been suggested as main drivers in the pathogenesis of COPD [6]. Among these pathogenic insults, the oxidative stress with an imbalance between oxidants and antioxidants has gained an increasing attention, which may provoke pathological reactions causing COPD [6]

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Results

Discussion

Conclusion