Tetraspanin 1 inhibits TNFα-induced apoptosis via NF-κB signaling pathway in alveolar epithelial cells
| Autor: | Gang Liu, Lawei Yang, Baoan Zou, Dehui Feng, Shenglan Gao, Zhanchun Pan, Ziying Lin, Yahong Wang, Changmei Huangfu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tetraspanins Pulmonary Fibrosis Immunology Apoptosis Lung injury Bleomycin 03 medical and health sciences chemistry.chemical_compound Idiopathic pulmonary fibrosis 0302 clinical medicine Tetraspanin Pulmonary fibrosis medicine Animals Humans RNA Small Interfering Cells Cultured Pharmacology Tumor Necrosis Factor-alpha NF-kappa B NF-κB respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL 030104 developmental biology chemistry 030220 oncology & carcinogenesis Alveolar Epithelial Cells Cancer research Tumor necrosis factor alpha Female Signal Transduction |
| Zdroj: | Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 67(11-12) |
| ISSN: | 1420-908X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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