Also, HMGB-1 is a mediator of inflammation, as a ligand of TLR2, TLR4, and RAGE (Park et al. 2004; Tian et al. 2007), that can promote ECM degradation and activate cell autophagy (Fu 2020), and it has been involved in various autoimmune diseases (e.g. rheumatoid arthritis (Schierbeck et al. 2013)). This evidence concerns the gene TLR4 and rheumatoid arthritis.