Tetraspanin 1 inhibits TNFα-induced apoptosis via NF-κB signaling pathway in alveolar epithelial cells
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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.
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.
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.
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.
KeywordsTetraspanin 1 Alveolar epithelial cells TNFα Apoptosis NF-κB
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).
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest.
- 25.Yang IV, Coldren CD, Leach SM, Seibold MA, Murphy E, Lin J, Rosen R, Neidermyer AJ, McKean DF, Groshong SD, Cool C, Cosgrove GP, Lynch DA, Brown KK, Schwarz MI, Fingerlin TE, Schwartz DA. Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis. Thorax. 2013;68(12):1114–21.CrossRefGoogle Scholar
- 29.Polla BS, Jacquier-Sarlin MR, Kantengwa S, Mariethoz E, Hennet T, Russo-Marie F, Cossarizza A. TNF alpha alters mitochondrial membrane potential in L929 but not in TNF alpha-resistant L929.12 cells: relationship with the expression of stress proteins, annexin 1 and superoxide dismutase activity. Free Radic Res. 1996;25(2):125–31.CrossRefGoogle Scholar