Montelukast improves bronchopulmonary dysplasia by inhibiting epithelial‑mesenchymal transition via inactivating the TGF‑β1/Smads signaling pathway.

Abstract

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 10mg/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 invitro. 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)‑β1 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‑β1‑ and hyperoxia‑induced AEC II cells. In addition, MK reduced the expression of Col I, MMP1, MMP3, TGF‑β1 and Smad3 in the lung tissues of the rat model of BPD, as well as in TGF‑β1‑ and hyperoxia‑induced AEC II cells. The present study demonstrated that MK improved BPD by inhibiting epithelial‑mesenchymal transition via inactivating the TGF‑β1/Smads signaling pathway.