Journal Article

Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair

Gherghe, Costin, Hamlett, Eric, Srikantha, Luxman, Rodgers, Laurel, Regan, Jenna N, Duan, Jinzhu, Rojas, Mauricio, Deb, Arjun, Liu, Dianxin, Majesky, Mark, Leask, Andrew, Willis, Monte

2012

نظرة عامة

Wnts are required for cardiogenesis but the role of specific Wnts in cardiac repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. Acute ischaemic cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by cardiac fibroblasts in the region of injury. Following cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired cardiac function and ventricular dilatation after cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in cardiac fibroblasts impairs wound healing and decreases cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving cardiac function after acute ischaemic cardiac injury. Wnt1/βcatenin signalling plays a critical role in cardiac repair following acute cardiac injury in vivo both by inducing cardiac fibroblast proliferation and by promoting epithelial–mesenchymal transition of the epicardium to generate cardiac fibroblast.

• الناشر: John Wiley & Sons, Ltd,Nature Publishing Group UK,Nature Publishing Group
• موضوع: Animals / beta Catenin - physiology / Cell Division / EMBO24 / EMBO37 / epicardium / Epithelial-Mesenchymal Transition / Fibroblasts - metabolism / Fibrosis / Gene Expression Regulation / Heart - physiology / In Situ Hybridization / ischaemia-reperfusion / Mice / Mice, Transgenic / Myocardial Infarction - genetics / Myocardial Infarction - metabolism / Myocardial Infarction - pathology / Pericardium - metabolism / Pericardium - pathology / Recombinant Fusion Proteins - physiology / Regeneration - physiology / repair / RNA, Small Interfering - pharmacology / Signal Transduction - physiology / Up-Regulation / Wnt / Wnt1 Protein - biosynthesis / Wnt1 Protein - genetics / Wnt1 Protein - physiology / Wound Healing - physiology