2. Academic Validation
  3. Entrectinib ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β1 signaling pathway

Entrectinib ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β1 signaling pathway

  • Int Immunopharmacol. 2022 Dec;113(Pt B):109427. doi: 10.1016/j.intimp.2022.109427.
Yang Miao 1,  Xiaohe Li 2,  Yue Yang 3,  Jianwei Zhang 4,  Li Chen 5,  Qianyi Zhang 6,  Wenqi Li 7,  Ying Liu 8,  Xianfeng Zhang 9,  Ruimin Gu 10,  Cheng Yang 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China. Electronic address: miaoyangtcm@163.com.
  • 2 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: lixiaohe908@163.com.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: 3306144286@qq.com.
  • 4 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: jianweizhang2021@163.com.
  • 5 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: 695988922@qq.com.
  • 6 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: 2945475189@qq.com.
  • 7 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China. Electronic address: 1120210653@mail.nankai.edu.cn.
  • 8 Department of Respiratory and Critical Care Medicine, Tianjin Beichen Hospital, No. 7 Beiyi Road, Beichen District, Tianjin 300400, People's Republic of China. Electronic address: 790384494@qq.com.
  • 9 Department of Respiratory and Critical Care Medicine, Tianjin Beichen Hospital, No. 7 Beiyi Road, Beichen District, Tianjin 300400, People's Republic of China. Electronic address: xianfengzhang@126.com.
  • 10 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China. Electronic address: guruimin@nankai.edu.cn.
  • 11 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 38 Tongyan Road, Haihe Education Park, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, People's Republic of China. Electronic address: cheng.yang@nankai.edu.cn.
PMID: 36375321 DOI: 10.1016/j.intimp.2022.109427
Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease with lesions confined to the lungs and is prevalent in the middle-aged and elderly population. The average survival time after diagnosis of IPF is only 3-5 years, and the mortality rate is higher than that of most tumours. IPF is called a "tumour-like disease". Entrectinib is a new oral formulation developed by Roche and was approved by the FDA to treat a wide variety of tumours. In this study, we explored the potential effects and mechanisms of entrectinib on pulmonary fibrosis in vitro and in vivo. In vivo studies showed that entrectinib is effective in alleviating bleomycin-induced pulmonary fibrosis. In vitro studies demonstrated that entrectinib dose-dependently inhibits TGF-β1/non-Smad signaling and attenuates TGF-β1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). In conclusion, entrectinib blocks TGF-β1-induced lung fibroblast activation and EMT and then attenuates bleomycin-induced pulmonary fibrosis in mice.

Keywords

EMT; Entrectinib; Fibroblasts; Pulmonary fibrosis; TGF-β signaling pathway.

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