Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury

@article{Bersell2009Neuregulin1ErbB4SI,
  title={Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury},
  author={Kevin Bersell and Shima Arab and Bernhard Haring and Bernhard K{\"u}hn},
  journal={Cell},
  year={2009},
  volume={138},
  pages={257-270}
}
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ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation
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The role of the NRG1 co-receptor ERBB2 in cardiac regeneration is explored using loss- and gain-of-function genetic tools, and it is shown that ER BB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
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A role for tissue-derived NRG in the regulation of EPC survival is suggested, as NRG treatment of eEPCs induces phosphorylation of kinases including Akt, GSK-3β, and Erk1/2 and the nuclear accumulation and transcriptional activation of β-catenin.
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It is suggested that ERBB4 overexpression potentiates MSC survival in the infarcted heart, enhances NRG1 generation to restore decliningNRG1 in theinfarcting region and stimulates cardiomyocyte division.
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Following heart injury, zebrafish dusp6 mutants show increased cardiomyocyte proliferation and angiogenesis and early downregulation of fibrosis genes, indicating accelerated cardiac repair associated with enhanced signaling via PDGFR and Nrg1/Erbb2.
Ephrin-B1 blocks adult cardiomyocyte proliferation and heart regeneration
TLDR
This work identifies ephrin-B1, a specific rod-shape stabilizer of the adult CM, as a natural padlock of adult CM proliferation for compensatory adaptation to different cardiac stresses (apectomy, MI, senescence), thus emphasizing a new link between the adultCM morphology and their proliferation potential.
Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart
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It is found that the metabolic reprogramming of border zone cardiomyocytes is induced by Nrg1/ErbB2 signaling and is important for their proliferation and is demonstrated that glycolysis regulatesCardiomyocyte proliferation during heart regeneration.
Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration
The key roles of ERBB2 in cardiac regeneration
TLDR
The findings establish that ERBB2 is necessary for NRG1-induced proliferation in neonatal cardiomyocytes, and that heart regeneration in fish is dependent on Erbb2 activity.
Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair
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It is shown that two TGF-β family members, Mstnb and Inhbaa, have opposite effects in regeneration, with mstnb overexpression or inhbaa loss-of-function causing cardiac scarring after injury.
Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish
TLDR
Evidence is found that Neuregulin1 (Nrg1), previously shown to have mitogenic effects on mammalian cardiomyocytes, is sharply induced in perivascular cells after injury to the adult zebrafish heart and is identified as a potent, induced mitogen for the endogenous adult heart regeneration program.
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References

SHOWING 1-10 OF 38 REFERENCES
Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells
TLDR
The results suggest that NRG-1 promotes cardiomyocyte differentiation of ESCs and the ErbB/PI3 K/Akt signaling pathway is one of the underlying molecular mechanisms.
Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair
TLDR
After myocardial infarction, periostin-induced cardiomyocyte cell-cycle reentry and mitosis were associated with improved ventricular remodeling and myocardials function, reduced fibrosis and infarct size, and increased angiogenesis.
Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes
TLDR
Observations suggest a mechanism whereby newt heart regeneration depends on the retention of proliferative potential in a subset of cardiomyocytes, similar to that described for their mammalian counterparts, as they arrest during mitosis or cytokinesis.
p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.
TLDR
It is shown that adult mammalian cardiomyocytes can divide and p38 is established as a key negative regulator ofCardiomyocyte proliferation and inhibition of p38 in adult cardiomers promotes cytokinesis.
FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction
TLDR
The data indicate that FGF1 and p38 MAP kinase, proteins involved in cardiomyocyte proliferation and angiogenesis during development, may be delivered therapeutically to enhance cardiac regeneration.
Cardiac myocyte cell cycle control in development, disease, and regeneration.
TLDR
The potential usefulness of cardiomyocyte self-renewal as well as feasibility of therapeutic manipulation of the cardiac myocyte cell cycle for cardiac regeneration are discussed.
Cyclin A2 Mediates Cardiomyocyte Mitosis in the Postmitotic Myocardium*
TLDR
It is reported that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood.
Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury
TLDR
Evidence is reported that stem cells or precursor cells contribute to the replacement of adult mammalian cardiomyocytes after injury but do not contribute significantly toCardiomyocyte renewal during normal aging.
Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.
  • Xifu Liu, X. Gu, M. Zhou
  • Medicine, Biology
    Journal of the American College of Cardiology
  • 2006
Requirement for neuregulin receptor erbB2 in neural and cardiac development
TLDR
The results demonstrate the importance of erbB2 in neural and cardiac development and find that mutant embryos die before Ell, probably as a result of dysfunctions associated with a lack of cardiac trabeculae.
...
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