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

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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.