Lawei Yang1, Yahong Wang1, Zhanchun Pan2, Shenglan Gao1, Bao'an Zou2, Ziying Lin3, Dehui Feng4, Changmei HuangFu4, Gang Liu5. 1. Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. 2. Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. 3. Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. linziying1988@126.com. 4. Elderly Medical Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China. 5. Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. gangliu11@gdmu.edu.cn.
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.
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. Murinepulmonary 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 IPFpatients. 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.
Authors: Josep M Lluis; Francesca Buricchi; Paola Chiarugi; Albert Morales; José C Fernandez-Checa Journal: Cancer Res Date: 2007-08-01 Impact factor: 12.701
Authors: Regina Golan-Gerstl; Shulamit B Wallach-Dayan; Philip Zisman; Wellington V Cardoso; Ronald H Goldstein; Raphael Breuer Journal: Am J Respir Cell Mol Biol Date: 2012-05-10 Impact factor: 6.914
Authors: Ivana V Yang; Christopher D Coldren; Sonia M Leach; Max A Seibold; Elissa Murphy; Jia Lin; Rachel Rosen; Amanda J Neidermyer; David F McKean; Steve D Groshong; Carlyne Cool; Gregory P Cosgrove; David A Lynch; Kevin K Brown; Marvin I Schwarz; Tasha E Fingerlin; David A Schwartz Journal: Thorax Date: 2013-06-19 Impact factor: 9.139