Establishment and dynamism of des-HMGB1, degraded HMGB1 by thrombin-thrombomodulin

我们之前发现HMGB1与血栓调节素（TM）结合，并在分子的n端被血栓调节素降解，并切割出10个氨基酸残基。我们将这种降解的HMGB1命名为des-HMGB1。我们还发现，des-HMGB1与其受体RAGE、toll样受体2和4的完整结合竞争，导致完整HMGB1及其受体信号传导的负调控。在本研究中，我们建立了des-HMGB1特异性ELISA，并研究了其在DIC、脓毒症和休克等多种疾病中的动态。我们发现，具有这些病理条件的患者血清中des-HMGB1升高，特别是在重组TM治疗的患者中。我们正在进一步研究des-HMGB1水平与TM治疗疗效及预后的关系。

We previously showed that HMGB1 binds to thrombomodulin(TM) and degraded by thrombin-TM at the N-terminus of the molecule cleaving out 10 aminoacdid-residue. We named this degraded HMGB1 as des-HMGB1. We also have showed that des-HMGB1 compete with intact binding to its receptor RAGE, Toll-like receptor-2 and-4 resulting negatively regulating of intact HMGB1 and its receptor signaling.In this study, we established the des-HMGB1 specific assay ELISA, and investigated its dynamism in various diseases including DIC, sepsis and shock. We showed that the des-HMGB1 was increased in the serum from the patients with these pathologic conditions, especially in the cases treated with recombinant TM. We are now further studying relationship between des-HMGB1 levels and the efficacy of TM treatment and their prognosis.