Tetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta-catenin pathway in human pulmonary fibrosis
Tetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta-catenin pathway in human pulmonary fibrosis
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Tetraspanin 1 作为纤维化介质抑制人肺纤维化中的 EMT 过程以及 Smad2/3 和 β-catenin 通路
DOI：
10.1111/jcmm.14258
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发表时间：
2019-05-01
影响因子：
5.3
通讯作者：
Lin, Ziying
中科院分区：
文献类型：
--
作者：
Liu, Gang;Wang, Yahong;Lin, Ziying
四联蛋白1（Tetraspanin 1, TSPAN1）作为癌症临床相关的基因靶点已被研究，但没有直接的体内或体外证据表明其与肺纤维化（PF）有关。通过重新分析基因表达Omnibus数据，我们首次发现特发性PF （IPF）患者肺组织中TSPAN1蛋白表达明显下调，并验证了IPF患者和博莱霉素诱导的PF小鼠肺组织样本中TSPAN1蛋白表达的降低。TSPAN1的表达降低，并与肺泡上皮细胞（AECs）中转化生长因子- β 1（tgf - β(1)）诱导的上皮-间质转化（EMT）的分子特征相关。在tgf - β(1)处理的aec中，沉默TSPAN1促进细胞迁移，α -平滑肌肌动蛋白、vimentin和E-cadherin的表达，而外源TSPAN1则具有相反的作用。此外，沉默TSPAN1可促进Smad2/3的磷酸化并稳定β -catenin蛋白，然而，过表达TSPAN1会阻碍tgf - β(1)诱导的aec中Smad2/3和β -catenin通路的激活。综上所述，我们的研究提示TSPAN1在IPF aec的EMT过程中起关键调节作用。
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 re-analysing 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-beta 1(TGF-beta(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-beta(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-beta(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.