Gremlin Enhances the Determined Path to Cardiomyogenesis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Jun 12

PMID 18545679

Citations 15

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methodology/principal Findings: 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.

Conclusions/significance: 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.

Citing Articles

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Wruck W, Bremmer F, Kotthoff M, Fichtner A, Skowron M, Schonberger S J Cell Mol Med. 2021; 25(3):1394-1405.

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Guo H, Zhao X, Su H, Ma C, Liu K, Kong S PeerJ. 2020; 8:e10502.

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