title: Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair.
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.
authors.affiliation: Department of Medicine, McAllister Heart Institute and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Duan
authors.forename: Costin
authors.initials: C
authors.lastname: Gherghe
authors.forename: Dianxin
authors.initials: D
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Hamlett
authors.forename: Luxman
authors.initials: L
authors.lastname: Srikantha
authors.forename: Laurel
authors.initials: L
authors.lastname: Rodgers
authors.forename: Jenna N
authors.initials: JN
authors.lastname: Regan
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.forename: Monte
authors.initials: M
authors.lastname: Willis
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
authors.forename: Mark
authors.initials: M
authors.lastname: Majesky
authors.forename: Arjun
authors.initials: A
authors.lastname: Deb
mesh_terms: D000818:Animals; D002455:Cell Division; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation; D051155:Wnt1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
chemical_list: C495267:CTNNB1 protein, mouse; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin
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