2009 Fiscal Year Final Research Report
Identification of human cardiomyogenic factor
| Project/Area Number |
18390116
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
UMEZAWA Akihiro National Research Institute for Child Health and Development, 生殖・細胞医療研究部, 部長 (70213486)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Junichi 国立成育医療センター(研究所), 名誉総長 (90051614)
MAKIHO Hatsune 国立成育医療センター(研究所), 生殖細胞医療研究部, 共同研究員 (90392498)
SAI Syoko 国立成育医療センター(研究所), 生殖細胞医療研究部, 共同研究員 (80392497)
AKUTSU Hidenori 国立成育医療センター(研究所), 生殖細胞医療研究部・生殖技術研究室, 室長 (50347225)
NASU Michiyo 国立成育医療センター(研究所), 生殖細胞医療研究部, 共同研究員 (80014116)
KURODA Masahiko 東京医科大学, 病理学研究室, 准教授 (80251304)
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| Project Period (FY) |
2006 – 2009
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| Keywords | 循環器 / 移植 / 再生医療 / 高血圧 / 液性因子 / バイオインフォマティックス |
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| Research Abstract |
The critical event in heart formation is commitment of mesodermal cells to a cardiomyogenic fate and their migration into anterolateral regions of the embryo during gastrulation. In this process, morphogenic movements and cardiac fate determination are regulated by cytokines. These secreted proteins play important roles in induction of cardiac transcription factors and differentiation of cardiomyocytes in amphibians and avians. Cardiomyogenic signals, indeed activate expression of cardiac specific transcriptional factors (Csx/Nkx2.5, Gata4, Mef2c), and these transcriptional factors activate expression of circulating hormones and cardiac specific proteins. Wnt family proteins have also been implicated in embryonic development, and cardiomyogenesis. In Drosophila, 'wingless', a homologue of vertebrate Wnt is involved in expression of 'tinman', through 'armadillo', and drives heart development. In vertebrates, however, Wnt1/3a, which activates the canonical Wnt/b-catenin signaling pathway leading to stabilization of b-catenin through inactivation of glycogen synthase kinase-3b, inhibits cardiomyocytic differentiation from cardiac mesoderm. Wnt11 promotes cardiac differentiation via the non-canonical pathway in Xenopus and murine embryonic cell lines. The secretion of Wnt inhibitors prevents Wnt3a secreted by the neural tube from inhibiting heart formation. In this study, we performed GeneChip analysis to identify multiple extracellular determinants, and evaluated the statistical significance of differential gene expression by NIA array analysis (http://lgsun.grc.nia.nih.gov/ANOVA/), a web-based tool for microarray data analysis. We found that Grem1 enhances the determined path to cardiomyogenesis, and that inhibition of the BMP signaling pathway is, at least in part, involved in initial determination of Grem1-promoted cardiomyogenesis.
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[Journal Article] Gremlin enhances the determined path to cardiomyogenesis.2008
Author(s)
Kami D, Shiojima I, Makino H, Matsumoto K, Takahashi Y, Ishii R, Naito AT, Toyoda M, Saito H, Watanabe M, Komuro I, Umezawa A
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Journal Title
PLoS One 3(6)
Pages: e2407
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[Journal Article] IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis.2008
Author(s)
Zhu W, Shiojima I, Ito Y, Li Z, Ikeda H, Yoshida M, Naito AT, Nishi J, Ueno H, Umezawa A, Minamino T, Nagai T, Kikuchi A, Asashima M, Komuro I
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Journal Title
Nature 454(7202)
Pages: 345-349
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