HMGB1 review: HMGB1 and Ischemia – reperfusion injury research

Introduction

Arterial bypass surgery, cardiopulmonary resuscitation, organ transplantation and other treatment applications, can make a variety of tissue and organ ischemia after blood reperfusion, although blood reperfusion is necessary for the survival of ischemic tissue conditions, but the reperfusion tissue may be excessive Oxygen free radicals, inflammatory factors and other tissue damage caused by further aggravated. HMGB1, a member of the damage associated molecular patterns (DAMP), has been shown to be involved in the development of multiple organ IRIs.

After liver tissue reperfusion, serum HMGB1 levels were observed to increase rapidly. The release of HMGB1 is associated with activation of the TLR4 receptor-dependent signaling pathway. Researchers have shown that the ASS-mediated cysteine-aspartic proteases (caspase)) 1 / interleukin (IL) -1 signaling can induce inflammation of the liver by promoting the release of HMGB1, leading to liver IRI. The use of IL-1? antibody in mice or mice with ASC gene deletion can decrease the expression level of HMGB1, Thereby reducing liver IRI. But the contradiction is that Izuishi et al found that the application of recombinant HMGB1 protein pretreated liver IRI model mice, model mice IRI was reduced. The expression of IL-1R-related kinase-M was elevated after pretreatment of recombinant HMGB1 protein, while IL-1R-related kinase-M was a negative regulator of TLR4 receptor. Therefore, HMGB1 on the liver IRI has two sides and its specific mechanism of action, yet to further study.

Immunohistochemistry and protein immunoblotting were used to detect the migration of HMGB1 to the cytoplasm in the nucleus of renal cells after renal ischemia and further release to the extracellular cells. The reperfusion could induce the release of HMGB1 into the renal tubules, capillaries and glomeruli. Kidney is more prone to IRI. After neutralization of HMGB1 antibody, renal IRI can be reduced to some extent, renal function can be improved. RAN et al. gave a carbon monoxide release molecule (CORM) -2 in mice 1 h before the establishment of mouse renal ischemia-reperfusion model, which significantly reduced IRI in mice kidney and increased survival after IRI Time and its renal function, the mechanism is that CORM-2 can reduce the activity of acetyltransferase in the nucleus of mice, so that the transfer and release of HMGB1 is almost completely inhibited.

Related Research

KamoN, KeB, GhaffariAA, et al. ASC/caspase-1/IL-1beta signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia/reperfusion injury. Hepatology, 2013,58(1):351–362.

Source: https://www.ncbi.nlm.nih.gov/pubmed/23408710

The ASC/Caspase-1/IL-1 signaling mediates inflammatory response by triggering HMGB1 induction in hepatic IRI. Their findings provide the rationale for a novel therapeutic strategy to manage liver injury due to IR.

Figure.Knockout of ASC signaling reduces HMGB1, TLR4-mediated inflammation, macrophage sequestration and innate cytokine/chemokine programs in IR-stressed livers

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