Lipopolysaccharide Stimulated the Migration of NIH3T3 Cells Through a Positive Feedback Between β-Catenin and COX-2

How beta-catenin/COX-2 contribute to inflammation- induced fibroblasts migration remains poorly understood. Therefore, in this study, lipopolysaccharide (LPS) was used as a stimulus to accelerate the migration of NIH3T3 cells, which mimicked the tissue repair process. LPS treatment increased the cell migration in concentration-and time-dependent manner. And NS398, a COX-2 inhibitor, inhibited LPS-induced NIH3T3 cells migration. DKK-1, an antagonist of the Wnt/beta-catenin signaling, also inhibited that migration. However, TWS119, an inducer of beta-catenin via GSK-3 beta, increased the cell migration. LPS or TWS119 treatment increased COX-2, beta-catenin, TGF-beta 1, and HMGB-1 expressions, and that could be attenuated by NS398 or DKK-1 addition. LPS induced the PGE(2) production, and PGE(2) increased the expression and nuclear translocation of beta-catenin, while EP2 blocker, AH6809, alleviated those effects. TWS119 increased the luciferase activity in the COX-2 promoter. In conclusion, LPS stimulated the NIH3T3 fibroblasts migration through a positive feedback between b-catenin and COX-2, in which PGE(2), EP2, TGF-beta 1, and HMGB-1 played as signal molecules.