• Qiang Zhang, Yuanyi Yue, and Rui Zheng.
• Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110014, China.
• Chin. Med. J. 2022 May 5; 135 (9): 1076-1086.

BackgroundFibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease (COPD). However, the key proteins involved in its development are still poorly understood. Thus, we aimed to identify the differentially expressed proteins (DEPs) between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung fibroblasts.MethodsThe potential DEPs were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The messenger RNA and protein levels of clusterin (CLU) in COPD patients and 12% cigarette smoke extract (CSE)-treated human bronchial epithelial cells were determined at the indicated time points. Furthermore, an in vitro COPD model was established via the administration of 8% CSE to normal human lung fibroblasts (NHLFs) at indicated time points. The effects of CSE treatment and CLU silencing on proliferation and activation of lung fibroblasts were analyzed.ResultsA total of 144 DEPs were identified between COPD patients and normal smokers. The iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker candidate. We also discovered that CLU levels were significantly increased ( P   <  0.0001) in Global Initiative for Obstructive Lung Disease II, III, and IV patients and correlated ( P   <  0.0001) with forced expiratory volume in 1 s ( R  = -0.7705), residual volume (RV) ( R  = 0.6281), RV/total lung capacity ( R  = 0.5454), and computerized tomography emphysema ( R  = 0.7878). Similarly, CLU levels were significantly increased in CSE-treated cells at indicated time points ( P  < 0.0001). The CSE treatment significantly inhibited the proliferation, promoted the inflammatory response, differentiation of NHLFs, and collagen matrix deposition, and induced the apoptosis of NHLFs; however, these effects were partially reversed by CLU silencing.ConclusionOur findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

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