| Literature DB >> 25848746 |
Gabriele D'Uva1, Alla Aharonov1, Mattia Lauriola2, David Kain3, Yfat Yahalom-Ronen1, Silvia Carvalho1, Karen Weisinger1, Elad Bassat1, Dana Rajchman1, Oren Yifa1, Marina Lysenko1, Tal Konfino3, Julius Hegesh4, Ori Brenner5, Michal Neeman1, Yosef Yarden1, Jonathan Leor3, Rachel Sarig1, Richard P Harvey6, Eldad Tzahor1.
Abstract
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.Entities:
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Year: 2015 PMID： 25848746 DOI： 10.1038/ncb3149
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824