[Role of histidine-rich glycoprotein as anti-DAMPs and therapeutic effects on DAMPs-related diseases].

Histidine-rich glycoprotein (HRG) is a plasma glycoprotein produced mainly in the liver. We have shown that HRG replacement therapy has a marked therapeutic effect on sepsis, in which high mobility group box 1 (HMGB1), one of the representative damage-associated molecular patterns (DAMPs), is known to play an important role in the disease progression. The mechanisms of action are diverse, including inhibition of immune thrombus formation and inhibition of ROS production. In addition, HRG has been shown to neutralize the toxicity of heme, a type of DAMPs, and neutralize the activity of LPS, a type of pathogen-associated molecular patterns (PAMPs), and to inhibit the translocation of HMGB1 from the nucleus of vascular endothelial cells to the extracellular space. Since DAMPs/PAMPs are known to play a central role in the pathogenesis of not only sepsis but also many inflammatory diseases, HRG has wide therapeutic applications and is considered to be a very promising seed for drug discovery.