Role of the extracellular signal-regulated kinase 1/2 signaling pathway in regulating the secretion of bronchial smooth muscle cells in a rat model of chronic asthma  

作　　者：XIE Min LIU Xian-sheng XU Yong-jian ZHANG Zhen-xiang BAI Jing NI Wang CHEN Shi-xin 

机构地区：[1]Department of Respiratory Medicine, Tongji Hospital Affiliated toTongji Medical College, Huazhong University of Science andTechnology, Wuhan, Hubei 430030, China

出　　处：《Chinese Medical Journal》2008年第1期73-77,共5页中华医学杂志（英文版）

基　　金：This study was supported by grants from National Natural Science Foundation of China （No. 30400195） and Dawn Program for Young Scientist of Wuhan （No. 20045006071-8）.

摘　　要：Background Although it is recognized that bronchial smooth muscle cells （BSMCs） play a key role. in airway remodeling during chronic asthma, it is not well understood how BSMCs exert their inflammatory functions. The extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway is an important signaling pathway in chronic asthma but its influence on secretion by BSMCs has not been well-studied. We investigated the impact of ERK1/2 signaling pathway on secretion by BSMCs in a rat model of chronic asthma in this study. Methods To create a rat model of chronic asthma, Wistar rats underwent ovalbumim （OVA） injection and eight weeks of inhalation. BSMCs were isolated and cultured in vitro. Epidermal growth factor, PD98059 and ERK1/2 antisense oligonucleotide were used to explore the role of ERK1/2 signaling pathway. The expression of P-ERK1/2 （phospho-ERK1/2） in BSMCs was analyzed by Western blot and reverse transcriptase-polymerase chain reaction （RT-PCR）. Secretion of BSMCs was detected by enzyme-linked immunosorbent assay （ELISA）. Results Phospho-ERK1/2 expression was increased in BSMCs of chronic asthmatic rats compared with the controls. PD98059 inhibited expression of phospho-ERK1/2 protein, while treatment with an antisense oligonucleotide inhibited the expression of P-ERK1/2 mRNA and protein. BSMCs obtained from the chronic asthma group secreted significantly greater quantities of growth factors （transforming growth factor （TGF）-β1, vascular endothelial growth factor （VEGF） and connective tissue growth factor （CTGF））, cytokines （regulated upon activation, normal T cell-expressed and secreted （RANTES） and eotaxin）, and extracellular matrix （fibronectin and collagen I） compared with normal controls. Epidermal growth factor stimulated secretion in both groups, but the response of the chronic asthma group was more intense. Both PD98059 and antisense oligonucleotide suppressed secretion by BSMCs in chronic ashmatic rats. Antisense oligonucleotide reduced tBackground Although it is recognized that bronchial smooth muscle cells （BSMCs） play a key role. in airway remodeling during chronic asthma, it is not well understood how BSMCs exert their inflammatory functions. The extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway is an important signaling pathway in chronic asthma but its influence on secretion by BSMCs has not been well-studied. We investigated the impact of ERK1/2 signaling pathway on secretion by BSMCs in a rat model of chronic asthma in this study. Methods To create a rat model of chronic asthma, Wistar rats underwent ovalbumim （OVA） injection and eight weeks of inhalation. BSMCs were isolated and cultured in vitro. Epidermal growth factor, PD98059 and ERK1/2 antisense oligonucleotide were used to explore the role of ERK1/2 signaling pathway. The expression of P-ERK1/2 （phospho-ERK1/2） in BSMCs was analyzed by Western blot and reverse transcriptase-polymerase chain reaction （RT-PCR）. Secretion of BSMCs was detected by enzyme-linked immunosorbent assay （ELISA）. Results Phospho-ERK1/2 expression was increased in BSMCs of chronic asthmatic rats compared with the controls. PD98059 inhibited expression of phospho-ERK1/2 protein, while treatment with an antisense oligonucleotide inhibited the expression of P-ERK1/2 mRNA and protein. BSMCs obtained from the chronic asthma group secreted significantly greater quantities of growth factors （transforming growth factor （TGF）-β1, vascular endothelial growth factor （VEGF） and connective tissue growth factor （CTGF））, cytokines （regulated upon activation, normal T cell-expressed and secreted （RANTES） and eotaxin）, and extracellular matrix （fibronectin and collagen I） compared with normal controls. Epidermal growth factor stimulated secretion in both groups, but the response of the chronic asthma group was more intense. Both PD98059 and antisense oligonucleotide suppressed secretion by BSMCs in chronic ashmatic rats. Antisense oligonucleotide reduced t

关 键 词：extracellular signal-regulated kinase ASTHMA bronchial smooth muscle cell SECRETION 

分 类 号：R562.25[医药卫生—呼吸系统]