蛋白酪氨酸磷酸酶Shp2调节香烟提取物诱导的肺上皮间质转化  

Shp2 regulates cigarette smoke extract-induced epithelial-mesenchymal transition

作　　者：沈辉娟[1] 蒋俊霞 李芬芬[2] 谢强敏[2] 颜小锋[1] SHEN Hui juan;JIANG Jun xia;LI Fen fen;XIE Qiang min;YAN Xiao feng(Dept of Pharmacy, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou310009, China;Dept of Basic Science of Medicine, College of Medicine, Zhejiang University, Hangzhou310058, China)

机构地区：[1]浙江大学医学院附属第二医院药剂科,浙江杭州310009 [2]浙江大学医学院基础医学部,浙江杭州310058

出　　处：《中国药理学通报》2017年第12期1673-1678,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973542)

摘　　要：目的探索蛋白酪氨酸磷酸酶Shp2对香烟烟雾提取物(cigarette smoke extract,CSE)诱导肺上皮间质转化(epithelial-mesenchymal transition,EMT)的调节作用。方法采用Q-PCR法和ELISA法探究Shp2抑制剂PHPS1对CSE诱导的肺上皮细胞转化生长因子β1(TGF-β1)表达的影响;免疫荧光染色法检测EMT相关因子的表达;Western blot法检测p-Shp2/Shp2、p-Smad2/Smad2的蛋白水平。结果 CSE诱导肺上皮细胞Shp2的激活,导致TGF-β1分泌释放增加,进而引起E-钙黏蛋白表达下调,以及波纹蛋白和α-肌动蛋白表达上调,这些变化可被Shp2抑制剂PHPS1抑制。抑制Shp2活性或表达可抑制CSE诱导的Smad2的磷酸化。结论Shp2调节CSE诱导的肺上皮间质转化可能通过Shp2/Smad2信号途径,提示Shp2可能是治疗肺癌和慢性阻塞性肺病新靶点。AimTo explore the effects of Shp2on cigarette smoke extract(CSE)induced epithelial mesenchymal transition(EMT).MethodsThe effects of CSE on TGFβ1levels in epithelial cells were measured by Q PCR and ELISA.Immunofluorescent staining was used to assess the expressions of CSE induced EMT related markers.The activation of CSE induced Shp2,Smad2was investigated by Western blot.ResultsCSE induced Shp2phosphorylation in a concentration dependent manner in A549cells.PHPS1inhibited the increase in mRNA and protein expression of TGFβ1induced by CSE.PHPS1regulated the expressions of CSE induced EMT markers(down regulation of E cadherin,up regulation expression of Vimentin andαSMA).The inhibition of either Shp2inhibitor or Shp2siRNA decreased Smad2phosphorylation induced by CSE.ConclusionsCSE initiates EMT through the Shp2/Smad2signaling pathway,which is activated by CSE through TGFβ1generation.It is suggested that Shp2might be a possible new target for COPD and lung cancer therapy.

关 键 词：上皮间质转化 转化生长因子Β1 香烟提取物 蛋白酪氨酸磷酸酶Shp2 慢性阻塞性肺病 肺癌 

分 类 号：R282.71[医药卫生—中药学] R322.35[医药卫生—中医学]