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学科主题临床医学
beta 2-Adrenoceptor Involved in Smoking-Induced Airway Mucus Hypersecretion through beta-Arrestin-Dependent Signaling
Zhou, Yujiao1,2,3; Zhang, Yuan1,2,3; Guo, Yang4; Zhang, Youyi1,2,3; Xu, Ming1,2,3; He, Bei1,2,3
刊名PLOS ONE
2014-06-06
DOI10.1371/journal.pone.0097788
9期:6
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]OBSTRUCTIVE PULMONARY-DISEASE ; CIGARETTE-SMOKE ; EPITHELIAL-CELLS ; GENE-EXPRESSION ; MURINE MODEL ; ACTIVATION ; RECEPTOR ; BLOCKERS ; INFLAMMATION ; PATHWAY
英文摘要

Progression of chronic obstructive pulmonary disease is associated with small airway obstruction by accumulation of inflammatory mucous exudates. However, the mechanism of mucin hypersecretion after exposure to cigarette smoke (CS) is still not clear. In this study, we explored the contribution of beta(2)-adrenoceptor (beta(2)-AR) signaling to CS extract (CSE)-induced mucus hypersecretion in vitro and examined the effect of a beta-blocker on airway mucin hypersecretion in vivo. NCI-H292 epithelial cell line was used to determine the contribution of beta(2)-AR signaling to CSE-induced MUC5AC production by treatment with beta(2)-AR antagonists propranolol and ICI118551 and beta(2)-AR-targeted small interfering RNA. The effect of propranolol on airway mucus hypersecretion was examined in a rat model exposed to CS. MUC5AC expression was assayed by real-time PCR, immunohistochemistry and ELISA. beta(2)-AR and its downstream signaling were detected by western blot analysis. We found that pretreating NCI-H292 cells with propranolol, ICI118551 for 30 min or beta(2)AR-targeted siRNA for 48 h reduced MUC5AC mRNA and protein levels stimulated by CSE. However, inhibiting the classical beta(2)AR-cAMP-PKA pathway didn′t attenuate CSE-induced MUC5AC production, while silencing beta-arretin2 expression significantly decreased ERK and p38MAPK phosphorylation, thus reduced the CSE-stimulated MUC5AC production. In vivo, we found that administration of propranolol (25 mg kg(-1) d(-1)) for 28 days significantly attenuated the airway goblet cell metaplasia, mucus hypersecretion and MUC5AC expression of rats exposed to CS. From the study, beta(2)-AR-beta-arrestin2-ERK1/2 signaling was required for CS-induced airway MUC5AC expression. Chronic propranolol administration ameliorated airway mucus hypersecretion and MUC5AC expression in smoking rats. The exploration of these mechanisms may contribute to the optimization of beta(2)-AR target therapy in chronic obstructive pulmonary disease.

语种英语
WOS记录号WOS:000341869000011
项目编号81270097 ; 30910103902 ; 81121061 ; 7112745 ; 20090001110093
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Ph.D. Programs Foundation of Ministry of Education of China
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52695
专题北京大学第三临床医学院_呼吸科
作者单位1.Changji Renmin Hosp, Dept Resp Med, Changji, Xinjiang, Peoples R China
2.Peking Univ, Hosp 3, Dept Resp Med, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100871, Peoples R China
4.Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Yujiao,Zhang, Yuan,Guo, Yang,et al. beta 2-Adrenoceptor Involved in Smoking-Induced Airway Mucus Hypersecretion through beta-Arrestin-Dependent Signaling[J]. PLOS ONE,2014,9(6).
APA Zhou, Yujiao,Zhang, Yuan,Guo, Yang,Zhang, Youyi,Xu, Ming,&He, Bei.(2014).beta 2-Adrenoceptor Involved in Smoking-Induced Airway Mucus Hypersecretion through beta-Arrestin-Dependent Signaling.PLOS ONE,9(6).
MLA Zhou, Yujiao,et al."beta 2-Adrenoceptor Involved in Smoking-Induced Airway Mucus Hypersecretion through beta-Arrestin-Dependent Signaling".PLOS ONE 9.6(2014).
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