Cucurbitacin E ameliorates airway remodelling by inhibiting nerve growth factor expression in nicotine‐treated bronchial epithelial cells and mice: The key role of let‐7c‐5p up‐regulated expression.

Cucurbitacin E (CuE) shows potential to handle airway remodelling. In the current study, the effects of CuE on nicotine‐induced airway remodelling were explored by focussing on its interaction with let‐7c‐5p/NGF axis. The potential microRNA (miR) as the therapeutic target for CuE treatment was determined using a microarray assay. Changes in viability, inflammation and let‐7c‐5p/NGF pathway in nicotine‐treated bronchial epithelial cells (BECs) were detected under CuE treatment (5 μM). The pathways were manipulated with let‐7c‐5p inhibitor. Mice were subjected to nicotine treatment and handled with CuE. Changes in pulmonary function and structure were detected. Based on the microarray data, let‐7c‐5p was selected as the therapeutic target. Viability and inflammation of BECs were induced by nicotine and then restored by CuE. At molecular level, nicotine suppressed let‐7c‐5p while induced NGF, FN1 and COLIA levels. The effects of CuE were counteracted by let‐7c‐5p inhibition. In a mouse model, nicotine impaired the function and structure of lung, which was attenuated by CuE and then re‐impaired by let‐7c‐5p antagomir. Collectively, CuE protected against nicotine‐induced airway remodelling and partially depended on the induction of let‐7c‐5p; our future work would pay more attention to other downstream effectors of the miR to promote the treatment of nicotine‐induced pulmonary disorders. [ABSTRACT FROM AUTHOR]