Nature cell biology, 2015-05, Vol.17 (5), p.627-638
2015
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- Autor(en) / Beteiligte
- Titel
- ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation
- Ist Teil von
- Nature cell biology, 2015-05, Vol.17 (5), p.627-638
- Ort / Verlag
- England
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/β-catenin signalling pathways. Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1465-7392eISSN: 1476-4679DOI: 10.1038/ncb3149Titel-ID: cdi_pubmed_primary_25848746
- Format
- –
- Schlagworte
- Age Factors, Animals, Animals, Newborn, beta Catenin - metabolism, Cell Dedifferentiation - drug effects, Cell Proliferation - drug effects, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases - metabolism, Glycogen Synthase Kinase 3 - metabolism, Glycogen Synthase Kinase 3 beta, Magnetic Resonance Imaging, Mice, Knockout, Myocardial Infarction - genetics, Myocardial Infarction - metabolism, Myocardial Infarction - pathology, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - metabolism, Myocytes, Cardiac - pathology, Neuregulin-1 - metabolism, Neuregulin-1 - pharmacology, Proto-Oncogene Proteins c-akt - metabolism, Receptor, ErbB-2 - agonists, Receptor, ErbB-2 - deficiency, Receptor, ErbB-2 - genetics, Receptor, ErbB-2 - metabolism, Regeneration - drug effects, Signal Transduction - drug effects, Time Factors, Time-Lapse Imaging