Newly identifi ed message for rescue and repair from necrotic cell: Biology and clinical relevance of“endokine, HMGB1”

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Responses to stimuli in cellar level are diverse and such hierarchical as secretion of stored factors,synthesis of lipid mediators and protein synthesis through genomic transcription. However, how can the cellsrespond in the case of necrosis? Recently a characteristic intranuclear protein, high-mobility group box 1 protein（HMGB1） is released from necrotic cells. The protein is an abundant nuclear protein with a dual functionboth inside and outside the cells. In physiological state, HMGB1 is present in the nucleus, and binds to DNA,playing a variety of crucial functions, including transcription and keeping the characteristic DNA architecture.However, the protein is released to extracellular space from most of necrotic cells, activated macrophages anddendritic cells. Out of the cells, HMGB1 acts as a signal of tissue damage and can promote infl ammation, immuneresponses, and results tissue regeneration. During sepsis and/or disseminated intravascular coagulation （DIC）,however, massive accumulation of HMGB1 in the systemic circulation will cause multiple organ failure （MOF）and subsequent lethal outcome. Thus HMGB1 in the systemic circulation has been considered as a lethalmediator of sepsis, and a promising therapeutic target for sepsis. Recently we identified that thrombomodulin（TM）, a natural anticoagulant glycoprotein expressed on the surface of endothelial cells, plays an importantrole in sequestering HMGB1. TM may prevent HMGB1 from reaching remote organs, thereby restrictingthe spectrum of HMGB1 action in the site of injury. Here we review recent progress made in defining thephysiological and pathological roles of HMGB1 and therapeutic strategies aimed at blocking circulatory HMGB1.

Newly identifi ed message for rescue and repair from necrotic cell: Biology and clinical relevance of“endokine, HMGB1”

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