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Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration. Dev Cell 2015 Aug 24;34(4):387-99

Date

08/11/2015

Pubmed ID

26256209

Pubmed Central ID

PMC4550513

DOI

10.1016/j.devcel.2015.06.017

Scopus ID

2-s2.0-84939777584 (requires institutional sign-in at Scopus site)   203 Citations

Abstract

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

Author List

Mahmoud AI, O'Meara CC, Gemberling M, Zhao L, Bryant DM, Zheng R, Gannon JB, Cai L, Choi WY, Egnaczyk GF, Burns CE, Burns CG, MacRae CA, Poss KD, Lee RT

Author

Caitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
Animals, Newborn
Cell Proliferation
Cholinergic Neurons
Denervation
Gene Expression Regulation
Heart
Immunity
Inflammation
Mice
Models, Biological
Molecular Sequence Data
Myocytes, Cardiac
Nerve Growth Factor
Neuregulin-1
Regeneration
Synaptic Transmission
Vagotomy
Zebrafish