Figure 4

Role of HMGB1 in hepatic pathology. (A) HBV and HCV infection confer a risk of developing a chronic inflammation that can lead to liver fibrosis and eventually evolve into liver cirrhosis and hepatocellular carcinoma, and HMGB1 participates in this process. HCV or HBV infection induces HMGB1 translocation and release. Extracellular HMGB1 causes chronic inflammation by activation of NF-κB pathways or results in TLR4-dependent interferon antiviral response. (B) Serum HMGB1 level is increased in several chronic liver diseases. HMGB1 induces HSC activation by TLR4-MyD88/MAPK-NF-κB pathways. HMGB1 promotes the expression of collagen and α-SMA in HSCs and results in accumulation of excess extracellular matrix and liver fibrosis. (C) Extracellular HMGB1 binds to its receptors (for example, TLR4, TLR9 and RAGE) to induce inflammasome activation and proinflammatory cytokine release, which is essential for tumor growth, invasion and metastasis.