High mobility group box 1 protein (HMGB1), a damage-associated molecular pattern, exists ubiquitously in the cells of mammals. It contributes to maintaining the structure of nucleosome and modulating transcription of gene in nuclei. Extracellular HMGB1 plays two-way roles in promoting inflammatory and tissue repair. Released actively as well as passively following cytokine stimulation during cell death, HMGB1 may act as a late inflammatory factor and an endogenous damage-associated molecular pattern recognized by its receptors. And it may mediate the occurrence, development and outcome of the inflammatory injury of digestive system diseases, such as gastric mucosal injury, inflammatory bowel-disease, liver injury, pancreatitis, and so on. This review mainly concerns the research progresses of HMGB1 in the inflammatory injury of digestive system diseases. At the same time, HMGB1 itself, or as a therapeutic target, can promote tissue repair.
ObjectiveTo observe the protective effect of tanshinone Ⅱ A on the mouse liver ischemia-reperfusion injury (IRI) model and preliminarily explore its mechanism of alleviating liver injury.MethodsThe IRI mouse model was established after the pre-treating with tanshinone Ⅱ A. Then, the serum and liver tissue of mice were collected to detect the changes of liver function, histopathology, liver cell apoptosis, and inflammatory factors. In addition, the protein expression levels of high mobility group box 1 (HMGB1), advanced glycosylation end-product specific receptor (RAGE), and Toll like receptor 4 (TLR4) in the liver tissues were detected by the Western blot method.ResultsAll data were analyzed by the homogeneity of variance test. The results of factorial design showed that the levels of ALT and AST in the serum, the pathological score and apoptosis index, the inflammatory response, as well as the expressions of HMGB1, TLR4 and RAGE proteins in the liver tissues were decreased significantly (P<0.05) in the sham operatation plus tanshinone Ⅱ A mice, which were increased significantly (P<0.05) in the IRI mice, which were antagonized synergistically by the tanshinone ⅡA and IRI (P<0.05).ConclusionsTanshinone ⅡA could reduce the liver IRI and inflammatory response in mouse. These effects might be related to the down-regulations of TLR4, HMGB1, and RAGE expressions.
ObjectiveTo investigate the protective effect and mechanism of curcumin on lipopolysaccharide (LPS)-induced acute lung injury.MethodsTotally 24 SD rats were randomly divided into a control group, a LPS group and a LPS+curcumin group (n=8 in each group). The degree of lung injury (oxygen partial pressure, wet/dry ratio, pathological scores) and inflammatory levels [tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, Toll-like receptor 4 (TLR4), mobility group box 1 protein (HMGB1) expression] of the lung were detected in different groups.ResultsOxygen partial pressure was significantly lower in the LPS group than that in the control group (P<0.05), while wet/dry ratio, pathological scores and expression levels of TNF-α, IL-6, MCP-1, TLR4 and HMGB1 were significantly higher in the LPS group than those in the control group (P<0.05). Compared with the LPS group, curcumin significantly reduced wet/dry ratio, pathological scores and expression levels of TNF-α, IL-6, MCP-1, TLR4 and HMGB1 in the LPS+curcumin group (P<0.05), while it significantly improved oxygen partial pressure (P<0.05).ConclusionCurcumin might protect LPS-induced acute lung injury through inhibition of TLR4-HMGB1-inflammation pathway.
ObjectiveTo explore the effect and potential mechanism of glycyrrhizin (GL) by inhibiting high mobility group box 1 (HMGB1) on glial scar formation after spinal cord injury (SCI) in rats.MethodsSeventy-two female Sprague Dawley rats were randomly divided into sham group (n=12), SCI model group (SCI group, n=36), GL intervention group (SCI+GL group, n=12), and nuclear factor κB (NF-κB) inhibitor [pynolidine dithiocarbamate (PDTC)] intervention group (SCI+PDTC group, n=12). The SCI models of SCI group, SCI+GL group, and SCI+PDTC group were made by modified Allen’s method, the sham group was only exposed the spinal cord without any injury. First of all, Basso-Beattie-Bresnahan (BBB) score of hind limbs and slope test were performed in SCI group at 1, 2, and 3 weeks after operation; Western blot was used to detect the expressions of glial fibrillary acidic protein (GFAP) and HMGB1 proteins. Compared with the sham group, the most significant time point in the SCI group was selected for subsequent experiment, in which the most significant glial scar was formed. Then, behavioral tests (BBB score of hind limbs and slope test), histological observation of spinal cord tissue structure, Western blot detection of HMGB1, GFAP, and NF-κB proteins, and immunohistochemical staining observation of GFAP and chondroitin sulfate proteoglycan (CSPG) were used to explore the effect of GL on the formation of glial scar after SCI and its potential mechanism.ResultsThe BBB score and slope angle of the SCI group increased gradually with time, which were significantly lower than those of the sham group at each time point (P<0.05). Western blot detection showed that the relative expressions of HMGB1 and GFAP proteins in the SCI group at 1, 2, and 3 weeks after operation were significantly higher than those in sham group (P<0.05). The change was most obvious at 3 weeks after SCI, therefore the spinal cord tissue was selected for subsequent experiments at this time point. At 3 weeks after operation, compared with the SCI group, BBB score and slope angle of SCI+GL group significantly increased (P<0.05); the relative expressions of HMGB1, GFAP, and NF-κB proteins detected by Western blot and the expressions of GFAP and CSPG proteins detected by immunohistochemical staining significantly decreased (P<0.05); the disorder of spinal cord tissue by HE staining improved, inflammatory cell infiltration reduced, and glial scar formation decreased. At 3 weeks after operation, the expressions of NF-κB, GFAP, and CSPG proteins of the SCI+PDTC group significantly reduced when compared with the SCI group (P<0.05); and the expression of NF-κB protein significantly decreased and the expressions of GFAP and CSPG proteins significantly increased when compared with the SCI+GL group (P<0.05).ConclusionAfter SCI in rats, the application of GL to inhibit the expression of HMGB1 can reduce the expression of GFAP and CSPG in the injured spinal cord, then reduce the formation of glial scars and promote the recovery of motor function of the hind limbs, and GL may play a role in inhibiting glial scar through HMGB1/NF-κB pathway.
High mobility group box 1 (HMGB1) is widely expressed in mammalian tissues and cells which is involved in various pathophysiological processes such as inflammation, autophagy, and apoptosis, and plays an important role in maintaining cell survival and normal function. HMGB1 plays an important part in the development of stroke, which can affect the prognosis by inducing neuroinflammation and autophagy. HMGB1 may have a bidirectional effect in acute and chronic phases. Exploring the specific role and mechanism of HMGB1 in each stage of stroke may make it a new target for prevention and treatment in the future.