FIGURE 1.

Fibrogenic secretome pathways implicated in the development of fibrosis and their dependence on SIRT1. Secretomic findings of DKK3 and Jagged1 are shown in red. DKK3 induces the Wnt pathway activating the frizzled receptor with its co-receptors LRP5/6. Further activation of the GSK3β leads to β-catenin nuclear translocation and therefore inducing the TCF/LEF family, target genes of the Wnt pathway. Jagged1 activates the Notch pathway with further NICD nuclear translocation and activation of Hes and Hey genes. Lack of SIRT1 leads to less degradation of NICD, which also leads to more β-catenin nuclear translocation, combining the Wnt and Notch pathway. Abbreviations: Wnt, wingless-related integration site – a signaling glycoprotein; Fz, frizzled receptor – a family of G protein-coupled receptor proteins serving as Wnt receptors; Disheveled – a family of cytoplasmic phosphoproteins downstream of frizzled receptors, which are involved in canonical and non-canonical Wnt signaling; NICD, notch intracellular domain; GSK3β, glycogen synthase kinase 3 beta; TCF/LEF family is a group of transcription factors involved in the Wnt signaling pathway; Hes, hairy and enhancer of split transcription factor protein; and Hey hairy/enhancer-of-split related transcription factor protein.