Figure 3.

Schematic graph showing that the complement system participates in the development of alcohol-induced liver disease. C3 convertase cleaves C3 to form C3a and C3b. ASP is the degraded product of C3a. C3b is an important component of C5 convertase. CR2-Crry is a site-targeted complement inhibitor that blocks all complement pathways at the C3 activation step. When anaphylatoxins C3a and C5a bind with their respective receptors, the TLR4/NF-κB pathway can be activated, resulting in the release of the inflammatory cytokine TNF-α, which participates in AFLD, either directly or indirectly, through the induction of insulin resistance. C3a and ASP bind to their receptor C5aR2 to promote the expression of Cyp2E1, which induces the production of ROS. The induced oxidative stress subsequently leads to the increased expression of Gly-tRF, which leads to AFLD via regulating the SIRT1 signaling pathway. The inflammatory response contributes to the development and progression of ALD. CR2, complement receptor 2; Crry, complement receptor 1-related protein y; ASP, acylation stimulating protein; Cyp2E1, cytochrome P450 family 2, subfamily E, polypeptide 1; GlytRFs, glycine tRNA-derived fragments; ROS, reactive oxygen species; TLR, toll-like receptor; TNF-α, tumor necrosis factor-alpha; AFLD, alcoholic fatty liver disease; ALD, alcohol-induced liver disease.