Roles of nuclear and extracellular HMGB1 in the pathogenesis of NAFLD (IMAGE)
Caption
Functional silencing of p53 promotes HMGB1 nucleocytoplasmic translocation. Then, HMGB1 triggers autophagy in hepatocytes by activating Beclin-1, facilitating lipid degradation. Nuclear HMGB1 also inhibits the LXRα/PPARγ axis, preventing liver steatosis. HC-HMGB1 can inhibit ER stress and prevent FFA β-oxidation. Conversely, extracellular HMGB1 stimulates the expression of TNF-α and IL-6 via the TLR4/MyD88 and RAGE/p-JNK/p-ERK signaling pathways. ↑, increase; ↓, decrease; BCL1, Beclin-1; ER, endoplasmic reticulum; FFA, free fatty acids; HMGB1, high-mobility group box-1; HC-HMGB1, hepatocyte-specific HMGB1; IL, interleukin; pJNK, phosphorylation of c-Jun N-terminal kinase; NAFLD, non-alcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; RAGE, receptor for advanced glycation end products; TLR, toll-like receptor; TNF, tumor necrosis factor.
Credit
Liang Peng, Lu Wang
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License
CC BY-NC