Hypoxia-inducible factor-1α regulates epithelial-to-mesenchymal transition in paraquat-induced pulmonary fibrosis by activating lysyl oxidase.

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.