典型文献
Clusterin as a serum biomarker candidate contributes to the lung fibroblasts activation in chronic obstructive pulmonary disease
文献摘要：
Background::Fibrosis 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.Methods::The 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.
Results::A 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.
Conclusion::Our findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.
文献关键词：
Chronic obstructive pulmonary disease;Clusterin;Cigarette smoke extract;Airway fibrosis;Lung fibroblasts
中图分类号：
作者姓名：
Zhang Qiang;Yue Yuanyi;Zheng Rui
作者机构：
Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110014, China;Department of Gastroenterology Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110014, China
文献出处：
引用格式：
[1]Zhang Qiang;Yue Yuanyi;Zheng Rui-.Clusterin as a serum biomarker candidate contributes to the lung fibroblasts activation in chronic obstructive pulmonary disease)[J].中华医学杂志（英文版）,2022(09):1076-1086
A类：
smoker,NHLFs
B类：
Clusterin,serum,biomarker,candidate,contributes,lung,fibroblasts,activation,chronic,obstructive,pulmonary,disease,Background,Fibrosis,peripheral,airways,airflow,limitation,patients,COPD,However,key,proteins,involved,its,development,still,poorly,understood,Thus,aimed,identify,differentially,expressed,DEPs,between,without,elucidate,molecular,mechanisms,by,investigating,effects,identified,Methods,potential,were,isobaric,tags,relative,absolute,quantitation,iTRAQ,analysis,messenger,levels,clusterin,CLU,cigarette,extract,CSE,treated,human,bronchial,epithelial,cells,determined,indicated,points,Furthermore,vitro,model,was,established,via,administration,normal,treatment,silencing,proliferation,analyzed,Results,total,smokers,proteomics,bioinformatics,analyses,We,also,discovered,that,significantly,increased,Global,Initiative,Obstructive,Lung,Disease,III,IV,correlated,forced,expiratory,volume,residual,RV,capacity,computerized,tomography,emphysema,Similarly,inhibited,promoted,inflammatory,response,differentiation,collagen,matrix,deposition,induced,apoptosis,however,these,partially,reversed,Conclusion,Our,findings,suggest,may,play,roles,during,fibrosis,regulating,Chronic,Cigarette,Airway
AB值：
0.504853
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