Dual faced HMGB1 plays multiple roles in cardiomyocyte senescence and cardiac inflammatory injury.

High mobility group box 1 (HMGB1) is constitutively expressed by many cells. In cells, HMGB1 is a transcription factor or transcription enhancer that is involved in nucleosome sliding, DNA repair, V(D)J recombination, telomere homeostasis, autophagy and viral sensing. HMGB1 can also be secreted or released by stressed cells and serves as an alarmin, cytokine or growth factor to activate the immune response. This protein facilitates CD4 T cell differentiation and tissue repair through binding with its receptors, including toll-like receptors (TLRs) and the receptor for advanced glycation end-products (RAGE). Recent works have established that HMGB1 plays many vital functions in cardiac inflammatory injury, cardiac regeneration and remodelling. The present review addresses the novel role of HMGB1 in secretion and cardiomyocyte senescence and in the dual faced roles of HMGB1 in cardiac inflammatory injury, inflammatory resolution and cardiac regeneration and remodelling following cardiac injury.