Open AccessTetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta‐catenin pathway in human pulmonary fibrosis
Author(s) -
Liu Gang,
Wang Yahong,
Yang Lawei,
Zou Baoan,
Gao Shenglan,
Song Zeqing,
Lin Ziying
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14258
Subject(s) - gene silencing , cancer research , epithelial–mesenchymal transition , pulmonary fibrosis , idiopathic pulmonary fibrosis , vimentin , beta catenin , gene knockdown , tetraspanin , bleomycin , ectopic expression , biology , catenin , transforming growth factor beta , fibrosis , microbiology and biotechnology , transforming growth factor , signal transduction , pathology , wnt signaling pathway , lung , medicine , cell , cancer , immunology , cell culture , gene , metastasis , immunohistochemistry , genetics , biochemistry , chemotherapy
Abstract Tetraspanin 1(TSPAN1) as a clinically relevant gene target in cancer has been studied, but there is no direct in vivo or vitro evidence for pulmonary fibrosis (PF). Using reanalysing Gene Expression Omnibus data, here, we show for the first time that TSPAN1 was markedly down‐regulated in lung tissue of patient with idiopathic PF (IPF) and verified the reduced protein expression of TSPAN1 in lung tissue samples of patient with IPF and bleomycin‐induced PF mice. The expression of TSPAN1 was decreased and associated with transforming growth factor‐β1 (TGF‐β 1 )‐induced molecular characteristics of epithelial‐to‐mesenchymal transition (EMT) in alveolar epithelial cells (AECs). Silencing TSPAN1 promoted cell migration, and the expression of alpha‐smooth muscle actin, vimentin and E‐cadherin in AECs with TGF‐β 1 treatment, while exogenous TSPAN1 has the converse effects. Moreover, silencing TSPAN1 promotes the phosphorylation of Smad2/3 and stabilizes beta‐catenin protein, however, overexpressed TSPAN1 impeded TGF‐β 1 ‐induced activation of Smad2/3 and beta‐catenin pathway in AECs. Together, our study implicates TSPAN1 as a key regulator in the process of EMT in AECs of IPF.