Extracellular HMGB1 acts on its target receptors (TLRs and RAGE) leading to nuclear translocation of transcription factors (e.g. NF-κB) and subsequent activation of innate immune responses which have been implicated in mediating several pathological conditions including sepsis32, liver33 and kidney ischemia reperfusion injury (IRI)34, acute lung injury35 and diabetes36. This evidence concerns the gene HMGB1 and ischemia.