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Fig. 2. The roles of ceramide and S1P in liver fibrosis. During liver fibrosis, ceramide and S1P levels are elevated. Ceramide promotes PKCζ activation, which induces CD36-mediated fatty acid uptake (Xia et al., 2015) and disturbs glucose uptake (Powell et al., 2003). Ceramide also stimulates CREB3L1 cleavage, which activates fibrogenic processes (Chen et al., 2016b; Denard et al., 2012). S1P induces Kupffer cell infiltration, which increases expressions of collagen and α-smooth muscle actin (Al Fadel et al., 2016; Friedman, 2008; Gonzalez-Fernandez et al., 2017). S1PR1 and S1PR3 is also involved in bone marrow-derived macrophage/monocytes migration to the liver (Li et al., 2011; Xiu et al., 2015). PKCζ, protein kinase C zeta; FFA, free fatty acids; CREB3L1, cAMP responsive element binding protein3 like 1; S1P, sphingosine 1-phosphate; MΦ, macrophage; αSMA, α-smooth muscle actin; S1PR, S1P receptor; BMM, bone marrow-derived macrophage/monocytes.
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