Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-beta 1 signalling pathway

Date

2019

Authors

Ruan, Hao
Lv, Ziwei
Liu, Shuaishuai
Zhang, Liang
Huang, Kai
Gao, Shaoyan
Gan, Wenhua
Liu, Xiaowei
Zhang, Shanshan
Helian, Kaiyue

Journal Title

Journal ISSN

Volume Title

Publisher

Pharmaceutical Press

Abstract

Objectives Anlotinib hydrochloride (AL3818) 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 TGFβ/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.

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Keywords

anlotinib, idiopathic pulmonary fibrosis, inflammation, oxidative stress, TGF-b signalling pathway

Citation

Source

Journal of Pharmacy and Pharmacology

Type

Journal article

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Restricted until

2099-12-31

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