Abstract
Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced PF. In addition, hypoxia-inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF-1α- and LOX-mediated regulation of EMT remains unclear. The present study investigated the association between HIF-1α and LOX with regard to PQ-induced EMT. A549 and RLE-6TN cells were treated with PQ, and HIF-1α and LOX expression was silenced with short interfering RNAs. Changes in the expression of HIF-1α, LOX, β-catenin and EMT-related makers were detected using real-time quantitative polymerase chain reaction, immunofluorescence, and western blotting. HIF-1α and LOX were associated with PQ-induced EMT, and their expression levels were significantly increased (P<0.05). LOX expression was significantly decreased following PQ poisoning when HIF-1α expression was inhibited (P<0.05). However, the level of HIF-1α did not change significantly when LOX was silenced. The expression level of β-catenin and the degree of EMT were significantly decreased following HIF-1α and LOX silencing in both cell lines (P<0.05). The association between HIF-1α and LOX in regulating EMT during PQ-induced PF may be unidirectional. HIF-1α may regulate PQ-induced EMT through the LOX/β-catenin pathway.