Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a

Abstract Background Arecoline is the main carcinogens in Areca nut that induce oral submucous fibrosis to develop into cancer. However, many previous studies have showed that Arecoline may inhibit proliferation and prevent collagen synthesis of fibroblasts. Results High dose Arecoline (> 32 µg/ml) could inhibit but low dose Arecoline (< 16 µg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was both sufficient and necessary for the promotion of fibrobasts proliferation. Egr-1, but not NF-κB, FOXO1, Smad2 or Smad3, mediated the expression of Wnt5a in fibrobasts. The specific siRNAs of Egr-1, Egr inhibitors or Wnt5a antibodies treatment blocked Arecoline induced Wnt5a upregulation and fibroblasts proliferation. Conclusions Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a, and Egr inhibitors or Wnt5a antibodies are potential therapeutic drugs of oral submucosal fibrosis and oral cancer.