HMGB1 and injury: 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.