Table 1.
Signal pathway-inflammatory mediator crosstalk network in liver fibrosis
| Crosstalk family member | Mechanism | Function in liver fibrosis | Biological basis as therapeutic target |
| TGF-β | Proliferation Migration Collagen production Crosstalk with small compounds Induces NK cell tolerance | Fibrosis activator | Deficiency of TGF-β inhibits liver fibrosis |
| Wnt/β-catenin | Promotes activation of HSC Collagen I production | Fibrosis activator | |
| TLR-2 TLR1/2 TLR2/6 | Activates NF-kB pathway Pro-inflammatory cytokines Activates Kupffer cell and IL-10 production | Inducer or suppressor in liver fibrosis | |
| TLR-3 | Crosstalk with IL-17A and γδT cell Crosstalk with CCL5 | Inducer or suppressor in liver fibrosis | Loss of TLR3 aggravates liver inflammation |
| TLR-4 | Pro-inflammatory cytokine production | Fibrosis activator | Inhibition of TLR4 promotes liver protection |
| TLR-5 | Crosstalk other pathway Regulates metabolism Anti-inflammatory cytokine production | Fibrosis inhibitor | Activation of TLR5 reduces liver fibrosis |
| TLR7 | Pro-inflammatory cytokine production Activates DCs Crosstalk with IFN signaling pathway | Fibrosis inhibitor | |
| TLR-9 | CXCL1 production Neutrophil infiltration | Fibrosis activator | |
| STAT3 | Crosstalk with IL-17, IL-10, and IL-6 Crosstalk with other signal pathways | Fibrosis activator or suppressor | Inhibition of STAT3 may inactivate HSCs and prevent liver fibrosis |
| miR-29b | Crosstalk with PI3K/AKT pathway Crosstalk with TGF-β1/SMAD3 pathway Induces HSC apoptosis | Fibrosis inhibitor | |
| miR-34a-5p | Crosstalk with TGF-β1/SMAD3 | Fibrosis inhibitor | |
| miR-130a-3p | Crosstalk with TGFBR1 and TGFBR2 Induces HSC apoptosis | Fibrosis inhibitor | |
| miR-19b | Crosstalk with HSC CCL2 | Fibrosis inhibitor | |
| miR-21 | Crosstalk with NLRP3 inflammasome/IL-1β axis | Fibrosis regulator | |
| miR-17-5p | Crosstalk with Wnt/β-catenin Activation of HSCs | Fibrosis promoter | |
| miR-142-3p | Crosstalk with TGF-β | Fibrosis inhibitor | |
| miR-200c | Crosstalk with PI3K/Akt | Fibrosis promoter | |
| miR-181b-3p | Crosstalk with TLR4 Kupffer cells | Fibrosis regulator | |
| miR-193a/b-3p | Inhibits activation of HSCs | Fibrosis regulator | |
| miR-26b-5p | Crosstalk with platelet-derived growth factor receptor-β | Fibrosis inhibition | |
| miR-219 | Crosstalk with TGF-βRII | Fibrosis inhibition | |
| miR-145 | Crosstalk with Krüppel-like factor 4 Promotes activation of HSCs | Fibrosis inhibition |
TGF-β: Transforming growth factor-β; TLR: Toll-like receptor; NF-кB: Nuclear factor-кB; HSC: Hepatic stellate cell; DCs: Dendritic cells; NK: Natural killer; IL: Interleukin.