β2-microglobulin as a biomarker of pulmonary fibrosis development in COPD patients.

Zhenchao Wu,Min Zhang,Youbo Fan,Can Ding,Guoyuan Ma,Mengdie Yan,Bingbing Wang,Nan Wu,Yi Liu,Xintong Du

doi:10.18632/aging.202266

Abstract

Expression of β2-microglobulin (β2M) is involved in fibrosis progression in kidney, liver, and heart. In this case-controlled retrospective study, we investigated the role of β2M in the development of pulmonary fibrosis in patients with chronic obstructive pulmonary disease (COPD). Analysis of 450 COPD patients revealed that patients with decreased pulmonary diffusing capacity (DLCO) had increased β2M serum levels. Compared to patients with lower β2M serum levels, patients with increased β2M levels exhibited increased alveolar wall/septal thickening and lung tissue β2M expression. In addition, patients with increased β2M levels had increased lung expression of TGF-β1, Smad4, and a-SMA. Animal experiments showed that increased β2M expression resulted in epithelial-mesenchymal transition (EMT), alveolar wall/septal thickening, and pulmonary fibrosis in a rat COPD model. Together, these results indicate that β2M serum levels may serve as a new indicator for assessment of pulmonary diffusion function and pulmonary fibrosis severity in clinical practice and may provide a potential target for treatment of pulmonary fibrosis in the future.

Highlights

D www.aging-us.com patients with emphysema have increased β2M levels in plasma and lungs, suggesting a potential involvement of lung macrophages [21]
Β2M levels differ in chronic obstructive pulmonary disease (COPD) patients with better and worse DLCO values
The COPD patients were divided into four groups according to their DLCO values

Summary

Introduction

D www.aging-us.com patients with emphysema have increased β2M levels in plasma and lungs, suggesting a potential involvement of lung macrophages [21]. Patients with moderate and severe COPD often have a decreased diffusion capacity and pulmonary fibrosis that might be mediated by an inflammatory factor, such as β2M. We tested the hypothesis that β2M promotes lung fibrosis in COPD patients, and that it may serve as a novel biomarker of pulmonary fibrosis development in COPD patients

Methods

Results

Conclusion