nsc-106399 and Airway-Remodeling

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.

Topics: Airway Remodeling; Animals; Epithelial Cells; Inflammation; Mice; MicroRNAs; Nerve Growth Factor; Nicotine; Triterpenes