D'Uva, Gabriele and Aharonov, Alla and Lauriola, Mattia and Kain, David and Yahalom-Ronen, Yfat and Carvalho, Silvia and Weisinger, Karen and Bassat, Elad and Rajchman, Dana and Yifa, Oren and Lysenko, Marina and Konfino, Tal and Hegesh, Julius and Brenner, Ori and Neeman, Michal and Yarden, Yosef and Leor, Jonathan and Sarig, Rachel and Harvey, Richard P and Tzahor, Eldad (2015) ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 17 (5). pp.627-38. ISSN 1476-4679 (Not OA)
Full text not available from this repository.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.
(NHMRC grants 573705; 573732 and the ARC Special Initiative in Stem Cell Science (Stem Cells Australia)).
| Item Type: | Article |
|---|---|
| Additional Information: | APRIL 2015 |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 21 Jan 2016 22:33 |
| Last Modified: | 05 Apr 2016 02:32 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/212 |
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