Identification of human cardiomyogenic factor

人类心肌生成因子的鉴定

• 批准号: 18390116
• 负责人: UMEZAWA Akihiro
• 金额: $ 11.82万
• 依托单位: National Research Institute for Child Health and Development
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390116/
• 关键词: 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; 移植・再生医療; 循環器・高血圧

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.

心脏形成的关键事件是中胚层细胞向心肌样细胞的命运的承诺和它们在原肠胚形成期间迁移到胚胎的前外侧区域。在这个过程中，形态发生运动和心脏命运决定由细胞因子调节。这些分泌蛋白在两栖类和鸟类心脏转录因子的诱导和心肌细胞的分化中起重要作用。心肌信号确实激活心脏特异性转录因子（Csx/Nkx2.5、Gata 4、Mef 2c）的表达，而这些转录因子激活循环激素和心脏特异性蛋白的表达。Wnt家族蛋白也与胚胎发育和心肌发生有关。在果蝇中，脊椎动物Wnt的同源物“无翅”通过“犰狳”参与“锡人”的表达，并驱动心脏发育。然而，在脊椎动物中，Wnt 1/3a激活经典的Wnt/β-连环蛋白信号通路，通过糖原合成酶激酶-3b的失活导致β-连环蛋白的稳定，抑制心肌细胞从心脏中胚层分化。Wnt 11通过非洲爪蟾和小鼠胚胎细胞系中的非经典途径促进心脏分化。Wnt抑制剂的分泌防止神经管分泌的Wnt 3a抑制心脏形成。在这项研究中，我们进行了基因芯片分析，以确定多种细胞外决定簇，并通过NIA阵列分析（http：//lgsun.grc.nia.nih.gov/ANOVA/），基于网络的微阵列数据分析工具，评估差异基因表达的统计学意义。我们发现Grem 1增强了确定的心肌发生途径，并且BMP信号通路的抑制至少部分地参与了Grem 1促进的心肌发生的初始确定。

项目成果

心筋細胞分化誘導促進剤及びその使用方法ピオグリタゾンを用いる

心肌细胞分化诱导促进剂及其使用方法

• 发表时间: 2009

Gremlin enhances the determined path to cardiomyogenesis.

• DOI: 10.1371/journal.pone.0002407
• 发表时间: 2008-06-11
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kami D;Shiojima I;Makino H;Matsumoto K;Takahashi Y;Ishii R;Naito AT;Toyoda M;Saito H;Watanabe M;Komuro I;Umezawa A
• 通讯作者: Umezawa A

心筋細胞分化誘導促進剤及びその使用方法テルミサルタン、バルサルタンを用いる

心肌细胞分化诱导促进剂及其使用方法 替米沙坦和缬沙坦

• 发表时间: 2007

Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells.

• DOI: 10.1016/j.yexcr.2006.11.012
• 发表时间: 2007-02
• 期刊: Experimental cell research
• 影响因子: 3.7
• 作者: Yoji Yamada;K. Sakurada;Yukiji Takeda;S. Gojo;A. Umezawa