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. 2011 Nov 28;590(Pt 3):447–458. doi: 10.1113/jphysiol.2011.219691

Figure 2. TLR4 signalling in hepatic stellate cells during liver fibrosis.

Figure 2

In chronic liver damage, intestinal permeability is increased due to systemic inflammation, portal hypertension, intestinal dysbiosis or tight junction disintegrity, which allows translocation of gut microflora-derived LPS into the liver through the portal vein. Translocated LPS stimulates TLR4 on hepatic stellate cells (HSCs). High expression of Bambi prevents TGF-β signalling in quiescent HSCs. Upon activation of TLR4, HSCs produce chemokines (MCP-1, MIP-1β and RANTES) that recruit Kupffer cells through CCR1 and CCR2. TLR4-activated HSCs downregulate Bambi and increase its sensitivity to TGF-β released from Kupffer cells. The fully activated TGF-β signalling then induces HSC activation. TLR4 signalling-mediated Bambi downregulation requires MyD88 and NF-κB.