Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors

Wnt signaling pathways and the intervention targets of Wnt pathway inhibitors. The secretion of Wnt proteins is dependent on palmitoylation by Porcupine. Frizzled and low-density lipoprotein receptor (LRP) proteins are membrane receptors for binding Wnt proteins. In the canonical Wnt pathway, Wnt binding leads to β-catenin nuclear translocation (after dissociation from a complex with Axin, glycogen synthase kinase 3β (GSK3β), adenomatous polyposis coli (APC) and casein kinase 1α (CK1α)), causing its interaction with TCF/LEF transcription factors and gene transcription. In the Wnt/PCP pathway, Wnt binding results in RhoA/ROCK and Rac/Jnk/NFAT pathway transduction. In the Wnt/Ca2+ pathway, Wnt binding leads to phospholipase C (PLC) activation and the accumulation of intracellular Ca2+, which then leads to the activation of calmodulin-dependent kinase II (CamKII), calcineurin and protein kinase C (PKC). UM206 targets the Frizzled receptor family; pyrvinium inhibits Axin degradation; ICG-001 inhibits the interaction between β-catenin and CBP; and WNT-974, CGX-1321 and GNF-6231 are porcupine inhibitor