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 (ca ERBB2) 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 ca ERBB2 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.
Vai all’articolo originale (in inglese): Gabriele D’Uva, Alla Aharonov, Mattia Lauriola, David Kain, Yfat Yahalom-Ronen, Silvia Carvalho, Karen Weisinger, Elad Bassat, Dana Rajchman, Oren Yifa, Marina Lysenko, Tal Konfino, Julius Hegesh, Ori Brenner, Michal Neeman, Yosef Yarden, Jonathan Leor, Rachel Sarig, Richard P Harvey and Eldad Tzahor. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 2015
Scientific recognitions
Science – News: New hope for heart attack sufferers?
NATURE – News and Views: Regenerative biology: Neuregulin 1 makes heart muscle
NATURE REVIEWS DRUG DISCOVERY – Research Highlight: Heart disease – Stimulating cardiomyocyte regeneration after heart failure
MEDIA COVERAGE
06.04.2015 – The Guardian: Heart muscle cells regrown in medical research breakthrough
06.04.2015 – The Sydney Morning Herald: Australian researchers help find way to regrow heart muscle
07.04.2015 – RT: Scientists discover revolutionary method to regrow heart muscles
07.04.2015 – AM: Helping the heart repair itself after a cardiac arrest: researchers say they’ve worked out how
07.04.2015 – Financial Express: The Turbo-charging hormone can repair ‘broken’ heart
07.04.2015 – El Comercio: Logran regenerar músculos del corazón al estimular una hormona
07.04.2015 – SKY NEWS: Breakthrough Sees Heart Muscle Cells Regrown
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07.04.2015 – The Jewish Press: Israeli-Australian Researchers Discover How to Regrow Heart Muscle
07.04.2015 – Business Magazin: STUDIU: Cercetătorii au reuşit să stimuleze regenerarea celulelor muşchiului cardiac
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13.04.2015 – EnlaceJudío: Científicos israelíes regeneran células cardíacas
13.04.2015 – israel21c: Weizmann Institute scientists regenerate heart cells in mice
13.04.2015 – IsraCast: Medical Breakthrough – Israeli Scientists Find Way to Regrow Heart Muscle Cells
13.04.2015 – Science Daily: Heart cells regenerated in mice
13.04.2015 – Popular Science: Scoperta la chiave per riparare il cuore infartuato
13.04.2015 – Science Codex: Heart cells regenerated in mice in NGR1 study
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14.04.2015 – ANI News: Regeneration of heart cells possible in mice
14.04.2015 – Business Standard: Regeneration of heart cells possible in mice
14.04.2015 – New Kerala: Regeneration of heart cells possible in mice
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14.04.2015 – Daily News & Analysis: Scientists regenerate heart cells in mice
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14.04.2015 – Iran Daily: Heart cells regenerated in mice
14.04.2015 – Horizon 2020 projects: ERC-funded research sees mouse heart cells renewed
14.04.2015 – Israeli Ministry of Foreign Affairs: Heart cells regenerated in mice
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14.04.2015 – DAILYROUNDS: Successful heart muscle regeneration in mice may soon be seen in humans
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18.04.2015 – Globus Magazine: RIGENERAZIONE CARDIACA: TROVATA LA CHIAVE PER RIPARARE IL CUORE INFARTUATO
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06.05.2015 – The Australian Jewish News: A heartening collaboration
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