Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis.
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| Abstract |
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 vivoAfter 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.
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| Authors | Sang-Hun Kim, Jung Yeon Lee, Chang Min Yoon, Hyeon Jun Shin, Sei Won Lee, Ivan Rosas, Erica Herzog, Charles S Dela Cruz, Naftali Kaminski, Min-Jong Kang |
| Journal | The European respiratory journal (Eur Respir J) Vol. 57 Issue 4 (04 2021) ISSN: 1399-3003 [Electronic] England |
| PMID | 33093124 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
| Copyright | Copyright ©ERS 2021. For reproduction rights and permissions contact [email protected]. |
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