RT期刊文章SR电子T1线粒体antiviral signaling protein is crucial for the development of pulmonary fibrosis JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2000652 DO 10.1183/13993003.00652-2020 VO 57 IS 4 A1 Kim, Sang-Hun A1 Lee, Jung Yeon A1 Yoon, Chang Min A1 Shin, Hyeon Jun A1 Lee, Sei Won A1 Rosas, Ivan A1 Herzog, Erica A1 Dela Cruz, Charles S. A1 Kaminski, Naftali A1 Kang, Min-Jong YR 2021 UL //www.qdcxjkg.com/content/57/4/2000652.abstract AB Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored.We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injury in vivo.After bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well.MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.MAVS may play a critical role in the development of pulmonary fibrosis, and targeting MAVS or its signalling by proapoptotic BH3 mimetics may be a feasible strategy for the treatment of IPF. https://bit.ly/31rIsmZ