Therapeutic Effects of the Bcl-2 Inhibitor on Bleomycin-induced Pulmonary Fibrosis in Mice

• DOI: 10.3389/fmolb.2021.645846
• Publication Date: 2021-10-08T20:07:44Z
• Authors: Yicheng He; Fei Li; Chao Zhang; Xinwei Geng; Madiha Zahra Syeda; Xufei Du; Zhehua Shao; Wen Hua; Wen Li; Zhihua Chen; Songmin Ying; Huahao Shen
• Keywords: 0301 basic medicine; 03 medical and health sciences; QH301-705.5; ABT-199; Bcl-2; Molecular Biosciences; macrophage; Biology (General); idiopathic pulmonary fibrosis; fibroblast; 3. Good health

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.