期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.645846
关键词
idiopathic pulmonary fibrosis; Bcl-2; ABT-199; macrophage; fibroblast
资金
- State Key Program of National Natural Science Foundation of China [81930003]
- National Natural Science Foundation of China [81870007]
- Funds for International Cooperation and Exchange of the National Natural Science Foundation of China [81920108001]
- Youth Foundation Project of Natural Science Foundation of Zhejiang Province of China [LQ18H010002]
Idiopathic pulmonary fibrosis (IPF) is a distressing lung disorder with limited therapeutic options. In this study, the therapeutic effect of Bcl-2 inhibitor ABT-199 on bleomycin-induced pulmonary fibrosis in mice was investigated. Early and late treatment with ABT-199 alleviated airway inflammation and lung fibrosis, suggesting it as a promising therapy for clinical IPF patients.
Idiopathic pulmonary fibrosis (IPF) is a distressing lung disorder with poor prognosis and high mortality rates. Limited therapeutic options for IPF is a major clinical challenge. Well-known for its anti-apoptotic properties, B-cell lymphoma 2 (Bcl-2) plays a critical role in the pathology of malignancies and inflammatory diseases, including IPF. In this study, we aimed to investigate the therapeutic effect of a Bcl-2 homology domain 3 mimetic inhibitor, ABT-199, on bleomycin (BLM)-induced pulmonary fibrosis in mice, and explore possible underlying mechanism. The lung inflammation and fibrosis model was established by intratracheal instillation of a single dose of BLM. We observed elevated Bcl-2 in the alveolar macrophages and fibroblasts derived from BLM-instilled mice from day 7. Further, we obtained in vivo evidence that early therapeutic treatment with Bcl-2 inhibitor ABT-199 from day 3, and late treatment from day 10, both alleviated airway inflammation and lung fibrosis induced by BLM. Our data suggest that ABT-199 might be an effective antifibrotic agent that interferes with profibrogenic cells, which may be a promising therapy in the treatment of clinical IPF patients.
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