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Tetraspanin 1 inhibits TNFα-induced apoptosis via NF-κB signaling pathway in alveolar epithelial cells

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Abstract

Objective

Tetraspanin family plays an important role in the pathogenesis of cancer, but its role in lung fibrosis is unknown. To determine whether tetraspanin 1 (TSPAN1), a member of the family, may be involved in the pathogenesis of pulmonary fibrosis.

Methods

TNFα -stimulated human alveolar epithelial (A549) and alveolar epithelial type II cell (AT2) were treated in vitro. Murine pulmonary fibrosis model was generated by injection of bleomycin (BLM). The expression of TSPAN1 was examined in vivo using the bleomycin-induced lung fibrosis model and tissue sample of IPF patients. Then we transfected the cells with TSPAN1 siRNA or plasmid and detected the expression changes of related proteins and cell apoptosis.

Results

In our study, we found that TSPAN1 was markedly down-regulated in lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and in bleomycin-induced pulmonary fibrosis in mice. We also found that TSPAN1 was significantly down-regulated in A549 and primary (AT2) cells following exposure to TNFα. Meanwhile, TSPAN1 inhibited p-IκBα, which attenuated nuclear NF-κB translocation and activation and inhibited apoptosis. We demonstrated that TSPAN1 reduced Bax translocation and caspase-3 activation, inhibited the apoptosis by regulating the NF-κB pathway in response to TNFα.

Conclusions

We conclude that TSPAN1 mediated apoptosis resistance of alveolar epithelial cells by regulating the NF-κB pathway. TSPAN1 may be a potential therapeutic target for pulmonary fibrosis or acute lung injury.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant nos. 81570062, 81600049 and 81172615); Guangdong Natural Science Foundation (Grant nos. 2016A030313681); Guangdong Medical Science Foundation (Grant nos. A2018134, A2017010, A2017027); Guangdong medical University scientific research fund (Grant nos. M2016001, M2016007, M2016022).

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Author notes

  1. Lawei Yang and Yahong Wang contributed equally to this work.

Authors and Affiliations

  1. Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

    Lawei Yang, Yahong Wang, Shenglan Gao, Ziying Lin & Gang Liu

  2. Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

    Zhanchun Pan & Bao’an Zou

  3. Elderly Medical Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China

    Dehui Feng & Changmei HuangFu

Authors
  1. Lawei Yang
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  2. Yahong Wang
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Corresponding authors

Correspondence to Ziying Lin or Gang Liu.

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Responsible Editor: John Di Battista.

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Yang, L., Wang, Y., Pan, Z. et al. Tetraspanin 1 inhibits TNFα-induced apoptosis via NF-κB signaling pathway in alveolar epithelial cells. Inflamm. Res. 67, 951–964 (2018). https://doi.org/10.1007/s00011-018-1189-9

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  • DOI: https://doi.org/10.1007/s00011-018-1189-9

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