The HMGB1-RAGE axis activates NF-κB to promote HPSE expression. MRC-5 cells were treated with 100 ng/ml HMGB1 alone, or combined with RAGE siRNA, or combined with NFκB inhibitor JSH-23 as described, and then subjected to following analyses. A. HMGB1 potently stimulated NF-κB subunit p65 nuclear translocation. B. ChIP assays revealed that NF-κB selectively binds to the HPSE promoter. C. Knockdown of RAGE by siRNA in MRC-5 cells repressed HMGB1 induced p65 nuclear translocation. D. Suppression of NF-κB activity by JSH-23 attenuated HMGB1 induced active and latent HPSE expression. *, p < 0.05; **, p < 0.01; and ***, p < 0.001.