Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

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Item Type:	Article
Title:	Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development
Creators Name:	Becker, J.R., Chatterjee, S., Robinson, T.Y., Bennett, J.S., Panáková, D., Galindo, C.L., Zhong, L., Shin, J.T., Coy, S.M., Kelly, A.E., Roden, D.M., Lim, C.C. and MacRae, C.A.
Abstract:	Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways.
Keywords:	ANP, BNP, Npr3, Cardiomyocyte Proliferation, Heart Development, Natriuretic Peptides, Animals, Zebrafish
Source:	Development
ISSN:	0950-1991
Publisher:	Company of Biologists
Volume:	141
Number:	2
Page Range:	335-345
Date:	January 2014
Official Publication:	https://doi.org/10.1242/dev.100370
PubMed:	View item in PubMed

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