Donglan Zhu1, Nan Ma1, Lin Chen1, Jinfu Huang1, Xiaoning Zhong2. 1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No 6 Shuangyong Road, Nanning, Guangxi 530021, China. 2. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No 6 Shuangyong Road, Nanning, Guangxi 530021, China. Electronic address: yeslyw@126.com.
Abstract
BACKGROUND: Aim of this study is investigates the influence of spiperone on hydrolase activity pathway in chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Differentially expressed genes (DEGs) were calculated by the limma package from microarray data GSE20257, and analysed via gene set enrichment analysis (GSEA) for identifying COPD related pathways. The regulation of hydrolase activity pathway related drugs was predicted by connectivity Map analysis (CMap). Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to investigate the effect of spiperone on regulation of hydrolase activity pathway in vitro experiment. RESULTS: A total of 378 DEGs were identified by the limma package. GSEA suggested that the regulation of hydrolase activity pathway was involved in the development of COPD. CMap of hub genes of regulation of hydrolase activity pathwayshown the most significant compound was spiperone. Results of vitro experiment verify that cigarette smoke extract (CSE) can increase the expression of fibronectin 1 (FN1) and epidermal growth factor (EGF), coinsided with decrease the expression of chemokine (C-X3-C motif) ligand 1 (CX3CL1), chemokoine (C-C motif) ligand 20 (CCL20), complement component 3 (C3) and slithomolog 2 (SLIT2) in BESA-2B cells and U937 cells. Spiperone can reverse the effect of CSE in BESA-2B cells and U937 cells. CONCLUSION: Regulation of hydrolase activity pathway was involved in the occurrence of COPD, spiperone was a potential drug for the treatment of COPD by affecting the regulation of hydrolase activity pathway. This study had provided new insights into the potential pathogenesis and treatment of COPD.
BACKGROUND: Aim of this study is investigates the influence of spiperone on hydrolase activity pathway in chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Differentially expressed genes (DEGs) were calculated by the limma package from microarray data GSE20257, and analysed via gene set enrichment analysis (GSEA) for identifying COPD related pathways. The regulation of hydrolase activity pathway related drugs was predicted by connectivity Map analysis (CMap). Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to investigate the effect of spiperone on regulation of hydrolase activity pathway in vitro experiment. RESULTS: A total of 378 DEGs were identified by the limma package. GSEA suggested that the regulation of hydrolase activity pathway was involved in the development of COPD. CMap of hub genes of regulation of hydrolase activity pathwayshown the most significant compound was spiperone. Results of vitro experiment verify that cigarette smoke extract (CSE) can increase the expression of fibronectin 1 (FN1) and epidermal growth factor (EGF), coinsided with decrease the expression of chemokine (C-X3-C motif) ligand 1 (CX3CL1), chemokoine (C-C motif) ligand 20 (CCL20), complement component 3 (C3) and slithomolog 2 (SLIT2) in BESA-2B cells and U937 cells. Spiperone can reverse the effect of CSE in BESA-2B cells and U937 cells. CONCLUSION: Regulation of hydrolase activity pathway was involved in the occurrence of COPD, spiperone was a potential drug for the treatment of COPD by affecting the regulation of hydrolase activity pathway. This study had provided new insights into the potential pathogenesis and treatment of COPD.