Merck

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

Developmental cell (2015-08-11)
Ahmed I Mahmoud, Caitlin C O'Meara, Matthew Gemberling, Long Zhao, Donald M Bryant, Ruimao Zheng, Joseph B Gannon, Lei Cai, Wen-Yee Choi, Gregory F Egnaczyk, Caroline E Burns, C Geoffrey Burns, Calum A MacRae, Kenneth D Poss, Richard T Lee
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Citric acid trisodium salt, anhydrous, ≥98% (GC)
Sigma-Aldrich
Citrate Concentrated Solution, BioUltra, for molecular biology, 1 M in H2O
Sigma-Aldrich
Citrate Concentrated Solution, BioReagent, suitable for coagulation assays, 4 % (w/v)
Sigma-Aldrich
o-Xylene, anhydrous, 97%