Wnt4 Is Crucial for Cardiac Repair by Regulating Mesenchymal-Endothelial Transition via the Phospho-JNK/JNK

The study investigated the role of Wnt4 in cardiac repair following acute cardiac ischemic reperfusion injury. It was found that Wnt4 was upregulated in cardiac fibroblasts near the injury site and facilitated mesenchymal-endothelial transition (MEndoT), which is beneficial for revascularizing damaged myocardium. Wnt4 acted as a downstream target of p53 and was crucial for MEndoT via the phospho-JNK/JNK signaling pathway, with both p53 and Wnt4 levels dependent on β-catenin signaling. Wnt4 knockdown worsened cardiac function, while its overexpression improved it by decreasing fibrosis and increasing vascular density. The study concluded that Wnt4 is vital for cardiac repair and a potential target for cardiac fibroblast-targeted therapy in heart disease.