BNP signaling is crucial for embryonic stem cell proliferation.

<h4>Background</h4>Embryonic stem (ES) cells have unlimited proliferation potential, and can differentiate into several cell types, which represent ideal sources for cell-based therapy. This high-level proliferative ability is attributed to an unusual type of cell cycle. The Signaling pa...

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Autores principales:	Essam Mohamed Abdelalim, Ikuo Tooyama
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78dc71b4f10f4a9481ae7dc8213480a5
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spelling	oai:doaj.org-article:78dc71b4f10f4a9481ae7dc8213480a52021-11-25T06:23:00ZBNP signaling is crucial for embryonic stem cell proliferation.1932-620310.1371/journal.pone.0005341https://doaj.org/article/78dc71b4f10f4a9481ae7dc8213480a52009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19399180/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Embryonic stem (ES) cells have unlimited proliferation potential, and can differentiate into several cell types, which represent ideal sources for cell-based therapy. This high-level proliferative ability is attributed to an unusual type of cell cycle. The Signaling pathways that regulate the proliferation of ES cells are of great interest.<h4>Methodology/principal findings</h4>In this study, we show that murine ES cells specifically express brain natriuretic peptide (BNP), and its signaling is essential for ES cell proliferation. We found that BNP and its receptor (NPR-A, natriuretic peptide receptor-A) were highly expressed in self-renewing murine ES cells, whereas the levels were markedly reduced after ES cell differentiation by the withdrawal of LIF. Targeting of BNP with short interfering RNA (siRNA) resulted in the inhibition of ES cell proliferation, as indicated by a marked reduction in the cell number and colony size, a significant reduction in DNA synthesis, and decreased numbers of cells in S phase. BNP knockdown in ES cells led to the up-regulation of gamma-aminobutyric acid receptor A (GABA(A)R) genes, and activation of phosphorylated histone (gamma-H2AX), which negatively affects ES cell proliferation. In addition, knockdown of BNP increased the rate of apoptosis and reduced the expression of the transcription factor Ets-1.<h4>Conclusions/significance</h4>Appropriate BNP expression is essential for the maintenance of ES cell propagation. These findings establish BNP as a novel endogenous regulator of ES cell proliferation.Essam Mohamed AbdelalimIkuo TooyamaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5341 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Essam Mohamed Abdelalim Ikuo Tooyama BNP signaling is crucial for embryonic stem cell proliferation.
description	<h4>Background</h4>Embryonic stem (ES) cells have unlimited proliferation potential, and can differentiate into several cell types, which represent ideal sources for cell-based therapy. This high-level proliferative ability is attributed to an unusual type of cell cycle. The Signaling pathways that regulate the proliferation of ES cells are of great interest.<h4>Methodology/principal findings</h4>In this study, we show that murine ES cells specifically express brain natriuretic peptide (BNP), and its signaling is essential for ES cell proliferation. We found that BNP and its receptor (NPR-A, natriuretic peptide receptor-A) were highly expressed in self-renewing murine ES cells, whereas the levels were markedly reduced after ES cell differentiation by the withdrawal of LIF. Targeting of BNP with short interfering RNA (siRNA) resulted in the inhibition of ES cell proliferation, as indicated by a marked reduction in the cell number and colony size, a significant reduction in DNA synthesis, and decreased numbers of cells in S phase. BNP knockdown in ES cells led to the up-regulation of gamma-aminobutyric acid receptor A (GABA(A)R) genes, and activation of phosphorylated histone (gamma-H2AX), which negatively affects ES cell proliferation. In addition, knockdown of BNP increased the rate of apoptosis and reduced the expression of the transcription factor Ets-1.<h4>Conclusions/significance</h4>Appropriate BNP expression is essential for the maintenance of ES cell propagation. These findings establish BNP as a novel endogenous regulator of ES cell proliferation.
format	article
author	Essam Mohamed Abdelalim Ikuo Tooyama
author_facet	Essam Mohamed Abdelalim Ikuo Tooyama
author_sort	Essam Mohamed Abdelalim
title	BNP signaling is crucial for embryonic stem cell proliferation.
title_short	BNP signaling is crucial for embryonic stem cell proliferation.
title_full	BNP signaling is crucial for embryonic stem cell proliferation.
title_fullStr	BNP signaling is crucial for embryonic stem cell proliferation.
title_full_unstemmed	BNP signaling is crucial for embryonic stem cell proliferation.
title_sort	bnp signaling is crucial for embryonic stem cell proliferation.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/78dc71b4f10f4a9481ae7dc8213480a5
work_keys_str_mv	AT essammohamedabdelalim bnpsignalingiscrucialforembryonicstemcellproliferation AT ikuotooyama bnpsignalingiscrucialforembryonicstemcellproliferation
_version_	1718413808939040768

BNP signaling is crucial for embryonic stem cell proliferation.

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