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학술저널
저자정보
Du Lijuan (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.D) Xu Changyi (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Tang Kun (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Shi Jia (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Tang Lu (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Lisha Xiao (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Lei Chengcheng (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Liu Huicong (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Liang Yuxia (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.) Guo Yubiao (Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen University Guangzhou China.Institute of Respiratory Diseases of Sun Yat-Sen University Guangzhou China.)
저널정보
대한천식알레르기학회(구 대한알레르기학회) Allergy, Asthma & Immunology Research Allergy, Asthma & Immunology Research Vol.15 No.3
발행연도
2023.5
수록면
374 - 394 (21page)
DOI
10.4168/aair.2023.15.3.374

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Purpose: Epithelial cystatin SN (CST1), a type 2 cysteine protease inhibitor, was significantly upregulated in asthma. In this study, we aimed to investigate the potential role and mechanism of CST1 in eosinophilic inflammation in asthma. Methods: Bioinformatics analysis on Gene Expression Omnibus datasets were used to explore the expression of CST1 in asthma. Sputum samples were collected from 76 asthmatics and 22 control subjects. CST1 mRNA and protein expression in the induced sputum were measured by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The possible function of CST1 was explored in ovalbumin (OVA)-induced eosinophilic asthma. Transcriptome sequencing (RNA-seq) was used to predict the possible regulated mechanism of CST1 in bronchial epithelial cells. Overexpression or knockdown of CST1 was further used to verify potential mechanisms in bronchial epithelial cells. Results: CST1 expression was significantly increased in the epithelial cells and induced sputum of asthma. Increased CST1 was significantly associated with eosinophilic indicators and T helper cytokines. CST1 aggravated airway eosinophilic inflammation in the OVA-induced asthma model. In addition, overexpression of CST1 significantly enhanced the phosphorylation of AKT and the expression of serpin peptidase inhibitor, clade B, member 2 (SERPINB2), while knockdown using anti-CST1 siRNA reversed the trend. Furthermore, AKT had a positive effect on SERPINB2 expression. Conclusions: Increased sputum CST1 may play a key role in the pathogenesis of asthma through involvement in eosinophilic and type 2 inflammation through activation of the AKT signaling pathway, further promoting SERPINB2 expression. Therefore, targeting CST1 might be of therapeutic value in treating asthma with severe and eosinophilic phenotypes.

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