Gremlin enhances the determined path to cardiomyogenesis.

<h4>Background</h4>The critical event in heart formation is commitment of mesodermal cells to a cardiomyogenic fate, and cardiac fate determination is regulated by a series of cytokines. Bone morphogenetic proteins (BMPs) and fibroblast growth factors have been shown to be involved in th...

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Autores principales: Daisuke Kami, Ichiro Shiojima, Hatsune Makino, Kenji Matsumoto, Yoriko Takahashi, Ryuga Ishii, Atsuhiko T Naito, Masashi Toyoda, Hirohisa Saito, Masatoshi Watanabe, Issei Komuro, Akihiro Umezawa
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Publicado: Public Library of Science (PLoS) 2008
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Acceso en línea:https://doaj.org/article/03c04e1e16af47eb8a864d3249975e5c
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spelling oai:doaj.org-article:03c04e1e16af47eb8a864d3249975e5c2021-11-25T06:12:05ZGremlin enhances the determined path to cardiomyogenesis.1932-620310.1371/journal.pone.0002407https://doaj.org/article/03c04e1e16af47eb8a864d3249975e5c2008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18545679/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The critical event in heart formation is commitment of mesodermal cells to a cardiomyogenic fate, and cardiac fate determination is regulated by a series of cytokines. Bone morphogenetic proteins (BMPs) and fibroblast growth factors have been shown to be involved in this process, however additional factors needs to be identified for the fate determination, especially at the early stage of cardiomyogenic development.<h4>Methodology/principal findings</h4>Global gene expression analysis using a series of human cells with a cardiomyogenic potential suggested Gremlin (Grem1) is a candidate gene responsible for in vitro cardiomyogenic differentiation. Grem1, a known BMP antagonist, enhanced DMSO-induced cardiomyogenesis of P19CL6 embryonal carcinoma cells (CL6 cells) 10-35 fold in an area of beating differentiated cardiomyocytes. The Grem1 action was most effective at the early differentiation stage when CL6 cells were destined to cardiomyogenesis, and was mediated through inhibition of BMP2. Furthermore, BMP2 inhibited Wnt/beta-catenin signaling that promoted CL6 cardiomyogenesis.<h4>Conclusions/significance</h4>Grem1 enhances the determined path to cardiomyogenesis in a stage-specific manner, and inhibition of the BMP signaling pathway is involved in initial determination of Grem1-promoted cardiomyogenesis. Our results shed new light on renewal of the cardiovascular system using Grem1 in human.Daisuke KamiIchiro ShiojimaHatsune MakinoKenji MatsumotoYoriko TakahashiRyuga IshiiAtsuhiko T NaitoMasashi ToyodaHirohisa SaitoMasatoshi WatanabeIssei KomuroAkihiro UmezawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2407 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daisuke Kami
Ichiro Shiojima
Hatsune Makino
Kenji Matsumoto
Yoriko Takahashi
Ryuga Ishii
Atsuhiko T Naito
Masashi Toyoda
Hirohisa Saito
Masatoshi Watanabe
Issei Komuro
Akihiro Umezawa
Gremlin enhances the determined path to cardiomyogenesis.
description <h4>Background</h4>The critical event in heart formation is commitment of mesodermal cells to a cardiomyogenic fate, and cardiac fate determination is regulated by a series of cytokines. Bone morphogenetic proteins (BMPs) and fibroblast growth factors have been shown to be involved in this process, however additional factors needs to be identified for the fate determination, especially at the early stage of cardiomyogenic development.<h4>Methodology/principal findings</h4>Global gene expression analysis using a series of human cells with a cardiomyogenic potential suggested Gremlin (Grem1) is a candidate gene responsible for in vitro cardiomyogenic differentiation. Grem1, a known BMP antagonist, enhanced DMSO-induced cardiomyogenesis of P19CL6 embryonal carcinoma cells (CL6 cells) 10-35 fold in an area of beating differentiated cardiomyocytes. The Grem1 action was most effective at the early differentiation stage when CL6 cells were destined to cardiomyogenesis, and was mediated through inhibition of BMP2. Furthermore, BMP2 inhibited Wnt/beta-catenin signaling that promoted CL6 cardiomyogenesis.<h4>Conclusions/significance</h4>Grem1 enhances the determined path to cardiomyogenesis in a stage-specific manner, and inhibition of the BMP signaling pathway is involved in initial determination of Grem1-promoted cardiomyogenesis. Our results shed new light on renewal of the cardiovascular system using Grem1 in human.
format article
author Daisuke Kami
Ichiro Shiojima
Hatsune Makino
Kenji Matsumoto
Yoriko Takahashi
Ryuga Ishii
Atsuhiko T Naito
Masashi Toyoda
Hirohisa Saito
Masatoshi Watanabe
Issei Komuro
Akihiro Umezawa
author_facet Daisuke Kami
Ichiro Shiojima
Hatsune Makino
Kenji Matsumoto
Yoriko Takahashi
Ryuga Ishii
Atsuhiko T Naito
Masashi Toyoda
Hirohisa Saito
Masatoshi Watanabe
Issei Komuro
Akihiro Umezawa
author_sort Daisuke Kami
title Gremlin enhances the determined path to cardiomyogenesis.
title_short Gremlin enhances the determined path to cardiomyogenesis.
title_full Gremlin enhances the determined path to cardiomyogenesis.
title_fullStr Gremlin enhances the determined path to cardiomyogenesis.
title_full_unstemmed Gremlin enhances the determined path to cardiomyogenesis.
title_sort gremlin enhances the determined path to cardiomyogenesis.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/03c04e1e16af47eb8a864d3249975e5c
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