HMGB1: A pleiotropic activity

Abstract

High-mobility group box 1 (HMGB1) is a high conserved nuclear protein (215 residues, 30 kD) encoded by a gene located on chromosome 13 (13q12), and it is part of high-mobility group (HMG)

Glycyrrhizic acid promotes sciatic nerves recovery in type 1 diabetic rats and protects Schwann cells from high glucose-induced cytotoxicity

“…High-mobility group box-1 (HMGB1), an evolutionarily conserved non-histone chromatin-binding protein, plays an important role in regulating nuclear homeostasis [ 12 ] . HMGB1 is actively excreted or passively discharged into the extracellular regions in response to specific stimulations, such as infection, injury, and sterile inflammation [ 12 – 13 ] .…”

“…High-mobility group box-1 (HMGB1), an evolutionarily conserved non-histone chromatin-binding protein, plays an important role in regulating nuclear homeostasis [ 12 ] . HMGB1 is actively excreted or passively discharged into the extracellular regions in response to specific stimulations, such as infection, injury, and sterile inflammation [ 12 – 13 ] . Extracellular HMGB1 has also been shown to promote nuclear factor Kappa Bp65 (NF-κBp65)-dependent cytokine production and establish a proinflammatory vicious circle to sustain the immune process via its receptors, ultimately leading to tissue damage [ 13 – 14 ] .…”

The Prothrombotic State Associated With Sars-Cov-2 Infection: Pathophysiological Aspects

“…HMGB1 displays strong proinflammatory properties in the extracellular milieu and is thought to play an essential role in numerous acute and chronic systemic inflammatory diseases, including sepsis. 36,97 In systemic inflammation, HMGB-1 levels rise into the circulation and in other biological fluids and exhibit a direct correlation with disease severity. In this context, two observations are of particular interest and suggest a possible involvement of this protein in microvascular thrombosis of different aetiologies: 1) the direct correlation between serum HMGB1 and severity of pneumonia caused by various agents, including viruses; 2) the capacity of HMGB1 to stimulate TF expression in monocytes and ECs and to reduce the activity of thrombin-TM complex with a consequent reduction in protein C activation.…”

“…In this context, two observations are of particular interest and suggest a possible involvement of this protein in microvascular thrombosis of different aetiologies: 1) the direct correlation between serum HMGB1 and severity of pneumonia caused by various agents, including viruses; 2) the capacity of HMGB1 to stimulate TF expression in monocytes and ECs and to reduce the activity of thrombin-TM complex with a consequent reduction in protein C activation. 36,97 In COVID-19 patients, the levels of serum HMGB1 are elevated and correlate with the severity of the disease and with a poor clinical outcome. 98,99 Moreover, in vitro, exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in a RAGE (receptor for advanced glycosylation end products)-dependent manner.…”

“…99 This mechanism adds to the known ability of HMGB1 to stimulate the production of inflammatory cytokines by immune cells (e.g., monocytesmacrophages) via TLRs. 97 Therefore, HMGB1 might play an important role in COVID-19, although more studies are required. Platelets.…”