Open AccessAnlotinib attenuated bleomycin‐induced pulmonary fibrosis via the TGF ‐β1 signalling pathway
Author(s) -
Ruan Hao,
Lv Ziwei,
Liu Shuaishuai,
Zhang Liang,
Huang Kai,
Gao Shaoyan,
Gan Wenhua,
Liu Xiaowei,
Zhang Shanshan,
Helian Kaiyue,
Li Xiaohe,
Zhou Honggang,
Yang Cheng
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13183
Subject(s) - pulmonary fibrosis , bleomycin , smad , idiopathic pulmonary fibrosis , cancer research , myofibroblast , fibrosis , chemistry , apoptosis , transforming growth factor , epithelial–mesenchymal transition , oxidative stress , lung , medicine , pathology , downregulation and upregulation , biochemistry , chemotherapy , gene
Objectives Anlotinib hydrochloride ( AL 3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin‐induced pulmonary fibrosis in mice and explored the antifibrosis mechanism. Methods We have evaluated the effect of anlotinib on bleomycin‐induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL ‐1β, IL ‐4, IL ‐6 and TNF ‐α were determined by ELISA . Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGF β/Smad3 and non‐Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF ‐β1‐induced epithelial–mesenchymal transition ( EMT ) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism. Key findings The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF ‐β1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF ‐β1‐induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts. Conclusions In summary, the results suggest that anlotinib‐mediated suppression of pulmonary fibrosis is related to the inhibition of TGF ‐β1 signalling pathway.