PLoS ONE (Jun 2008)

Gremlin enhances the determined path to cardiomyogenesis.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0002407
Journal volume & issue
Vol. 3, no. 6
p. e2407

Abstract

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BackgroundThe 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.Methodology/principal findingsGlobal 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.Conclusions/significanceGrem1 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.