Inhibiting the Translocation of HMGB1 Alleviates Renal Ischemia–Reperfusion Injury by Cutting Down Inflammatory Cascade

Abstract

Background

Ischemia and reperfusion does damage to tissues and causes the decline of organ function though the inflammatory cascade. Noteworthy, HMGB1 possess a crucial role in promoting progression of these effects in kidney. The study aimed at ascertaining the concrete mechanism of HMGB1 triggering inflammatory cascade in renal ischemia–reperfusion injury (IRI).

Methods

IRI was induced in mice by clamping left renal arteries for 60 minutes followed by 24 hours of reperfusion with the removal of right kidney. The effects of HMGB1on IRI were evaluated by targeting creatinine, blood urea nitrogen, survival rates, renal morphology, and the translocation and secretion of HMGB1. In addition, the expression of Toll-like receptor 4, phosphorylated nuclear factor κB p65, nuclear factor κB p65, and inflammatory cascade molecules (interleukin [IL]-1β, and IL-6, and tumor necrosis factor-α) were carried out.

Results

Our results demonstrated that antibody against HMGB1 (anti-HMGB1) can improve the survival rate; decrease the expression of creatinine, blood urea nitrogen, Toll-like receptor 4, phosphorylated nuclear factor κB p65, IL-1β, IL-6, and tumor necrosis factor-α; reduce renal pathological injury; alleviate the secretion of HMGB1; and suppress the translocation of HMGB1 from nucleus into cytoplasm in IRI. Notably, recombinant HMGB1, the agonist of HMGB1, can alleviate the noted effects of anti-HMGB1 in IRI.

Conclusion

HMGB1 can aggravate renal IRI by triggering the inflammatory cascade, the mechanism of which is associated with activating the Toll-like receptor 4–nuclear factor κB p65 signal pathway.