Montelukast improves bronchopulmonary dysplasia by inhibiting epithelial-mesenchymal transition via inactivating the TGF-1/Smads signaling pathway

The present study investigated the role of montelukast (MK) during the progression of bronchopulmonary dysplasia (BPD) and the underlying mechanism of action. A rat model of BPD was induced by hyperoxia and subsequently, the rats were treated with 10 mg/kg MK. On day 14 post-hyperoxia induction, lung function was assessed by detecting the mean linear intercept (MLI; the average alveolar diameter), the radial alveolar count (RAC; alveolar septation and alveologenesis) and the lung weight/body weight (LW/BW) ratio. Type II alveolar epithelial (AEC II) cells were isolated from normal rats to investigate the mechanism underlying the effect of MK on BPD in vitro. Western blotting and reverse transcription-quantitative PCR were performed to measure the expression levels of surfactant protein C (SP-C), E-cadherin, N-cadherin, Vimentin, collagen I (Col I), matrix metallopeptidase (MMP)1/3, transforming growth factor (TGF)-beta 1 and Smad3. MK significantly reduced the MLI and the LW/BW ratio, and increased the RAC of the BPD group compared with the control group. MK upregulated the expression of SP-C and E-cadherin, and downregulated the expression levels of N-cadherin and Vimentin in the lung tissues of the rat model of BPD, as well as in TGF-beta 1- and hyperoxia-induced AEC II cells. In addition, MK reduced the expression of Col I, MMP1, MMP3, TGF-beta 1 and Smad3 in the lung tissues of the rat model of BPD, as well as in TGF-beta 1- and hyperoxia-induced AEC II cells. The present study demonstrated that MK improved BPD by inhibiting epithelial-mesenchymal transition via inactivating the TGF-beta 1/Smads signaling pathway.