Correlation between sestrin2 expression and airway remodeling in COPD

Da-Wei Zhang,Yuan-Yuan Wei,Shuang Ji,Guang-He Fei

doi:10.1186/s12890-020-01329-x

Abstract

BackgroundAirway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified.MethodsA total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed.ResultsIn patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT.ConclusionIncreased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.

Highlights

Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress
HE staining demonstrated that the airway epithelial structure and ciliated cells were intact in the control group, while the ciliated cells were detached and lodged to different degrees in the COPD group (Fig. 1a)
Continuous Rbm was clearly observed in the control group, but the reticular basement membrane was fragmentary in the COPD group based on PASM staining (Fig. 1c)

Summary

Introduction

Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Excessive oxidative stress contributes to enhanced airway remodeling and inversely correlates with lung function in patients with COPD [5, 6].Sestrins, a family of highly conserved proteins, are induced by oxidative and persistent hypoxia and expressed in the lung, brain, liver, heart and many other organs [7, 8]. Human tissue can better reflect the real pathological characteristics of the occurrence and development of this disease.

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