Atorvastatin attenuates paraquat poisoning-induced epithelial-mesenchymal transition via downregulating hypoxia-inducible factor-1 alpha

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 alpha). 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 (alpha-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 alpha and beta-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 alpha-SMA and vimentin in both lung tissues and in vitro cell culture. In addition, ATS treatment may decrease the HIF-1 alpha and beta-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 alpha/beta-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.