Figure 6.

The mechanism of Lyso-ER cholesterol-transport-regulated macrophage polarization in HBx-related NASH. In HBx-induced ox-LDL-dependent NASH-associated inflammatory responses, the PGE2-EP4-mTOR signaling axis regulated NPC1-ORP5 interactions mediating Lyso-ER cholesterol transport. ER-redox-dependent ER stress induced by ER cholesterol is involved in mediating the M1 polarization of macrophages. The targeted intervention of EP4 rescues MC polarization imbalance to improve the NASH phenotype in HBx-Tg mice. The red arrows indicate the index was increased and the blue arrows indicate the index was decreased in this study.