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Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model

XIAO Jun WANG Ke FENG Yu-lin CHEN Xue-rong XU Dan ZHANG Ming-ke

中华医学杂志(英文版)2011,Vol.124Issue(20):3327-3333,7.
中华医学杂志(英文版)2011,Vol.124Issue(20):3327-3333,7.DOI:10.3760/cma.i.issn.0366-6999.2011.20.022

Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model

Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model

XIAO Jun 1WANG Ke 2FENG Yu-lin 1CHEN Xue-rong 2XU Dan 1ZHANG Ming-ke2

作者信息

  • 1. Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China
  • 2. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041,China
  • 折叠

摘要

Abstract

Background Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease,which is closely associated with cigarette smoking.However,the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known.This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 (ERK 1/2) in airway mucus hypersecretion induced by cigarette smoke in rats.Methods A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks.Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126,a specific MEK1 kinase inhibitor,at doses of 0.25 mg/kg,0.5 mg/kg and 1 mg/kg for 14 days.Expression of MUC5AC mRNA and protein,ERK 1/2 and phosphorylated-ERK 1/2 (p-ERK 1/2) were detected by RT-PCR,immunohistochemistry and Western blotting.Results Cigarette smoke significantly increased airway goblet cells metaplasia,induced the overexpression of MUG5AC mRNA and protein in bronchial epithelia,and increased the ratio of p-ERK 1/2 and ERK 1/2.U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke (P <0.05).Moreover,there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein (P<0.05).Conclusions Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein.ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo.

关键词

extracellular signal-regulated kinase 1/2/mucus hypersecretion/MUC5AC

Key words

extracellular signal-regulated kinase 1/2/mucus hypersecretion/MUC5AC

引用本文复制引用

XIAO Jun,WANG Ke,FENG Yu-lin,CHEN Xue-rong,XU Dan,ZHANG Ming-ke..Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model[J].中华医学杂志(英文版),2011,124(20):3327-3333,7.

基金项目

This study was supported by a grant from China Postdoctoral Science Foundation (No.37508). (No.37508)

中华医学杂志(英文版)

OACSCDCSTPCD

0366-6999

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