Anlotinib inhibits the benign airway stricture scar tissue by regulating YAP
X. Zhenga (Ms), Y. Cheng*a (Dr)
a Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, CHINA
Background: Benign tracheal stenosis is prone to recurrence due to the proliferation of granulation scar tissue, making tracheal stenosis a clinical problem. Therefore, there is a need to find a new method for the treatment. Objective: To investigate the inhibitory effect of anlotinib on tissue formation and fibroblast proliferation in airway scar tissue. Methods: In vivo: The model of tracheal stenosis was established by scratching the airway in rats with a nylon brush. Anlotinib or normal saline was administered for 7 days. The rats were sacrificed on the 14th day after the operation and the trachea was removed. HE staining was used to observe the scar tissue. In vitro: human lung fibroblasts (MRC-5 cells) with/without anlotinib treatment or TGF-β induction, were used. The ability of proliferation and migration of MRC-5 were detected by CCK-8 and cell scratch assays. The protein expression level of Collagen I was detected by western blot and the nucleoplasmic localization of YAP by cell immunofluorescence assay . Results: In vivo: Compared with the normal saline group, the granulation scar tissue reduced after anlotinib treatment. In vitro: (1) Compared with the TGF-β alone group, anlotinib inhibited the proliferation of fibroblasts. (2) Compared with the TGF-β alone group, the anlotinib group inhibited the migration of fibroblasts. (3) Compared with TGF-β alone group, the expression of Collagen I decreased in anlotinib group. (4) Compared with the control group, TGF-β promoted the nuclear translocation of YAP. Compared with the TGF-β alone group, the anlotinib group inhibited the nuclear translocation of YAP. Conclusion: Anlotinib can attenuate the formation of benign airway stricture scar tissue and inhibit TGF-β-induced fibroblast proliferation, migration and up-regulation of extracellular matrix protein expression, which may be achieved by inhibiting YAP nuclear translocation. To provide a new option for the treatment of benign airway stenosis.
Disclosure of funding source(s): none