LAUSR

Aim: This study investigated the effects of atorvastatin (ATS) on the paraquat (PQ)‐induced epithelial‐mesenchymal transition (EMT) and the potential mechanism through hypoxia‐inducible factor‐1 alpha (HIF‐1&agr;). Main methods: Sprague–Dawley (SD) rats were randomly divided into a control group (n = 5), PQ group (n = 20), PQ + ATS L group (n = 20, ATS 20 mg/kg daily) and PQ + ATS H group (n = 20, ATS 40 mg/kg daily). All treated rats were given a 20% PQ solution (50 mg/kg) once by gavage and then sacrificed 12, 24, 72 and 168 h after PQ exposure. The A549 and RLE‐6TN cell lines were treated with ATS, PQ or both for 24 h. Mesenchymal (&agr;‐SMA and vimentin) and epithelial (E‐cadherin and ZO‐1) cell marker expression was tested both in vivo and in vitro. The effects of ATS on HIF‐1&agr; and &bgr;‐catenin expression were also evaluated. Key findings: ATS alleviated PQ poisoning‐induced lung injury and pulmonary fibrosis in vivo. This effect was dose‐dependent. ATS treatment attenuated the EMT by increasing the levels of the epithelial markers E‐cadherin and ZO‐1 and by decreasing the expression of the mesenchymal markers &agr;‐SMA and vimentin in both lung tissues and in vitro cell culture. In addition, ATS treatment may decrease the HIF‐1&agr; and &bgr;‐catenin levels both in vivo and in vitro. Significance: In conclusion, ATS can attenuate PQ‐induced pulmonary fibrosis. The mechanism may involve the downregulation of the HIF‐1&agr;/&bgr;‐catenin pathway and the inhibition of the PQ‐induced EMT by ATS. ATS may be considered as a therapeutic agent for PQ poisoning‐induced pulmonary fibrosis.