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

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

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)429-442
Number of pages14
JournalEMBO Journal
Volume31
Issue number2
DOIs
StatePublished - Jan 18 2012
Externally publishedYes

Keywords

  • Wnt
  • epicardium
  • fibrosis
  • ischaemia-reperfusion
  • repair

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Duan, J., Gherghe, C., Liu, D., Hamlett, E., Srikantha, L., Rodgers, L., Regan, J. N., Rojas, M., Willis, M., Leask, A., Majesky, M., & Deb, A. (2012). Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. EMBO Journal, 31(2), 429-442. https://doi.org/10.1038/emboj.2011.418