Figure 5.

Canonical WNT/β-catenin signaling in cardiac fibrosis. In the absence of Wnt ligands, cytosolic β-catenin is degraded by the destruction complex, which includes Axin and adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)-3β and casein kinase (CK)1, protein phosphatase 2A (PP2A), and β-transducin repeat-containing protein (β-TrCP). After a Wnt ligand binds to the receptor Frizzled (Fz) and the receptor-related protein 5 or 6 (LRP5/6) coreceptor, the Wnt–Fz–LRP5/6 complex recruits Disheveled (DVL) and Axin through the intracellular domains of Fz and LRP5/6, resulting in β-catenin stabilization. The increased nuclear levels of β-catenin promote interaction with T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor to regulate Wnt-responsive fibrotic genes.