Fig. 3: Multifaceted roles of Nur77 in liver disease.

This schematic cartoon illustrates Nur77’s regulatory functions across liver pathologies, highlighting its therapeutic relevance. In liver inflammation, Nur77 inhibits NF-κB signaling, reduces pro-inflammatory cytokines, and supports anti-inflammatory M2 macrophage polarization. In fibrosis, Nur77 inhibits HSC activation and antagonizes the TGF-β–Smad2/3/4–ZEB signaling pathway, leading to reduced extracellular matrix proteins, e.g., fibronectin, α-SMA. In lipid metabolism and steatosis, Nur77 attenuates lipid uptake and lipogenesis while enhancing fatty acid oxidation through FGF21, thereby reducing hepatic triglyceride and cholesterol levels. In the context of HCC and tumor immunity, Nur77 exerts tumor-suppressive effects by modulating glycolysis (via PEPCK1, WFDC21P) and inhibiting β-catenin, reduces HK1 palmitoylation in HSCs ( ↓ glycolytic EVs), restores CAR-T/NK cell function, promotes immunosuppressive TME via high TI-Treg expression, and its inhibition boosts anti-tumor immunity via IFN-I^Mo/NK cell activation^{50,51,52,53,55,56,57,60,61,65,72,75,76}.