Shp2 regulates cigarette smoke extract-induced epithelial-mesenchymal transition

VernacularTitle: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
Author: juan Hui SHEN ¹ ; xia Jun JIANG ; fen Fen LI ; min Qiang XIE ; feng Xiao YAN
Author Information

1. 浙江大学医学院附属第二医院药剂科
Keywords: epithelial-mesenchymal transition; TGF-β1; cigarette smoke extract; Shp2; COPD; lung canc-er
From: Chinese Pharmacological Bulletin 2017;33(12):1673-1678
CountryChina
Language:Chinese
Abstract: Aim To explore the effects of Shp2 on cig-arette smoke extract (CSE)-induced epithelial-mesen-chymal transition (EMT). Methods The effects of CSE on TGF-β1 levels in epithelial cells were meas-ured by Q-PCR and ELISA. Immunofluorescent stai-ning was used to assess the expressions of CSE-induced EMT-related markers. The activation of CSE-induced Shp2,Smad2 was investigated by Western blot. Re-sults CSE induced Shp2 phosphorylation in a concen-tration-dependent manner in A549 cells. PHPS1 inhib-ited the increase in mRNA and protein expression of TGF-β1 induced by CSE. PHPS1 regulated the expres-sions of CSE-induced EMT markers (down-regulation of E-cadherin,up-regulation expression of Vimentin and α-SMA). The inhibition of either Shp2 inhibitor or Shp2 siRNA decreased Smad2 phosphorylation induced by CSE. Conclusions CSE initiates EMT through the Shp2 / Smad2 signaling pathway,which is activated by CSE through TGF-β1 generation. It is suggested that Shp2 might be a possible new target for COPD and lung cancer therapy.