Fig. 6: The ANGPTL8 interaction with the LILRB2/PIRB receptor regulates the ERK pathway in HCC cells and Fgr expression in Kupffer cells.

A Schematic diagram of the PIR receptor interaction with ANGPTL8 based on the chimeric luciferase receptor system. B The interaction between ANGPTL8 and PIRs was detected using a chimeric luciferase receptor assay (n = 4 per group). Data are the mean ± SD. Statistical comparisons were performed using Student’s t test. *p < 0.05, **p < 0.01. C ANGPTL8 and LILRB2/PIRB expression in HepG2 and RAW264.7 cells detected by immunofluorescence using ANGPTL8-Flag and LILRB2/PIRB-GFP plasmids. Scale bar, 40 μm. D P-ERK, ERK, LC3II/I, ATG5, P62 and Beclin-1 expression detected by western blotting in (a) MHCC97H, (b) HepG2, (c) WT, and (d) ANGPTL8-KO (d) primary mouse hepatocytes with ANGPTL8 OE or rANGPTL8 during blocking using an anti-LILRB2/PIRB antibody. Protein expression was normalized to β-actin or β-tubulin, and the numbers represent the mean ± SD of an average of 3 independent experiments. E Representative images of cellular immunofluorescence staining of Fgr in RAW264.7 cells with or without rANGPTL8 and PIRB antibody treatment. Scale bar, 100 μm. F Schematic representation of the mechanism by which ANGPTL8 accelerates hepatocarcinogenesis by promoting tumor cell proliferation and modulating macrophage polarization to facilitate immune escape.