High-mobility group box 1 protein and its role in severe acute pancreatitis

Table 2 Relationship between high mobility group box 1 protein and severe acute pancreatitis

Ref.	Journal	Country	Subject	Method	Result
Yasuda et al[75]	Pancreas	Japan	Patients with SAP	Control group: healthy volunteers (n = 8); Experimental group: patients with SAP (n = 45)	Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity
Kocsis et al[78]	Pancreatol	Hungary	Patients with AP	Control group: healthy volunteers (n = 20); AP group: patients with pancreatitis and divided into mild (n = 32) and severe (n = 30) subgroups; Sepsis group: patients with sepsis (n = 20)	HMGB1 was significantly elevated in the plasma of SAP patients compared with healthy and mild pancreatitis patients, and was correlated with procalcitonin concentrations. There was an inverse correlation between the levels of sRAGE and HMGB1 in patients with SAP. Circulating DNA was significantly elevated in patients with severe pancreatitis or sepsis and was related to the severity scores
Lindström et al[80]	Pancreas	Finland	Patients with AP	Grade 0: mild AP (n = 282); Grade 1: SAP without organ failure (n = 135); Grade 2: SAP with organ failure (n = 38)	Serum HMGB1 level is comparable in three groups, but sRAGE is significantly higher in AP patients who develop organ failure compared to AP patients who recover without organ failure
Yuan et al[84]	Pancreas	China	Male ICR mice	Control group: SAP mice (n = 24); Treatment group: SAP mice treated with recombinant HMGB1 A box protein 12 (n = 12) and 24 h (n = 12) after the modeling injection	HMGB1 A box can decrease the serum HMGB1 levels, attenuate organ dysfunction and improve the survival of SAP mice. Thus, it has a remarkable protective effect against pancreatitis and associated organ injury
Luan et al[82]	Immunobiol	China	Male Wistar rats	Control group: sham operation; SAP group: SAP-induced rats; Treated groups: SAP-induced rats treated with pRNA-U6.1/Neo-HMGB1 (containing siRNA targeting human HMGB1)	Downregulation of HMGB1 by using siRNA could inhibit the activation of NF-κB in SAP rats so as to decrease the levels of downstream inflammatory cytokines, alleviate endothelial permeability and attenuate severe pancreatitis-associated acute lung injury
Kang et al[86]	Gastroenterol	United States	HMGB1 flox/flox and Pdx1-Cre transgenic mice	AP group: AP-induced mice; Control group: administered with saline as a control	Deficiency of endogenous HMGB1 could escalate local inflammation through destabilization of the nucleus and enable rapid DNA and histone release, resulting in accelerated tissue injury and lethality, indicating that intracellular HMGB1 appears to have a protective effect against inflammation

AP: Acute pancreatitis; HMGB1: High mobility group box 1 protein; SAP: Severe acute pancreatitis; sRAGE: Soluble receptors for advanced glycation end-products.