Journal
INFLAMMATION RESEARCH
Volume 67, Issue 11-12, Pages 951-964Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-018-1189-9
Keywords
Tetraspanin 1; Alveolar epithelial cells; TNF; Apoptosis; NF-B
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Funding
- National Natural Science Foundation of China [81570062, 81172615, 81600049] Funding Source: Medline
- Natural Science Foundation of Guangdong Province [2016A030313681] Funding Source: Medline
- Medical Science and Technology Foundation of Guangdong Province [A2017010, A2017027, A2018134] Funding Source: Medline
- Guangdong Medical University Scientific research fund [M2016007, M2016001] Funding Source: Medline
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ObjectiveTetraspanin 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.MethodsTNF -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.ResultsIn 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 TNF. Meanwhile, TSPAN1 inhibited p-IB, which attenuated nuclear NF-B translocation and activation and inhibited apoptosis. We demonstrated that TSPAN1 reduced Bax translocation and caspase-3 activation, inhibited the apoptosis by regulating the NF-B pathway in response to TNF.ConclusionsWe conclude that TSPAN1 mediated apoptosis resistance of alveolar epithelial cells by regulating the NF-B pathway. TSPAN1 may be a potential therapeutic target for pulmonary fibrosis or acute lung injury.
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