Figure 5.

Toll-like receptor signaling drives liver fibrosis through activation of hepatic stellate cells. In chronic liver damage, intestinal permeability is increased due to systemic inflammation, portal hypertension, intestinal dysbiosis, or tight junction disintegrity, leading to bacterial translocation. Translocated LPS stimulates TLR4 on HSCs. Upon activation of TLR4, HSCs produce chemokines to recruit Kupffer cells through CCR1 and CCR2, and Bambi is downregulated through MyD88 and NF-κB. The fully activated TGF-β signaling eventually induces HSC activation and liver fibrosis. TLR4 also inhibits miR-29 to enhance collagen production. CCR5 is important for HSC recruitment. Generally, the NK cells-TLR3-IFNΓ axis suppresses HSC activation.