Role of calcium signaling on the hepatic and pancreatic stem cells in the animal model of metabolic syndrome during childhood.

钙信号传导对儿童期代谢综合征动物模型中肝和胰腺干细胞的作用。

• 批准号: 20591226
• 负责人: NAKAMURA Kimitoshi
• 金额: $ 2.91万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591226/
• 关键词: メタボリック症候群; 幹細胞; 内胚葉; カルシウムシグナル; メタボリックシンドローム; トランスジェニックマウス; 内胚葉系幹細胞; 肝細胞; ルタボリック症候群

Calreticulin(CRT) is a Ca2+-binding protein of the endoplasmic reticulum and essential for cardiac development. Cardiac-specific overexpression of calreticulin by α-myosin heavy chain promoter results in complete heart block and sudden death in transgenic mice. Here, to investigate further mechanism of calreticulin, we generate transgenic mice that cause temporal and spatial overexpression of calreticulin using cre-loxP system. The mice were cross-bred with Nkx2.5-Cre mice which express cre recombinase under control of Nkx2.5 promoter, a transcription factor essential for early cardiac development. Overexpression of calreticulin was associated with PR interval and QRS interval prolongation, bradycardia, sudden death between 6-week-old and 10-week-old. Furthermore, some of the NKx2.5-CRT transgenic mice revealed marked edema in 7-week-old. In conclusion, overexpression calreticulin in the heart is associated with a decrease in HCN1 expression and calreticulin plays an important role of HCN1 gene regulation.

钙网蛋白（CRT）是内质网的钙结合蛋白，对心脏发育至关重要。α-肌球蛋白重链启动子介导的钙网蛋白心脏特异性过表达导致转基因小鼠完全性心脏传导阻滞和猝死在这里，为了进一步研究钙网蛋白的机制，我们使用cre-loxP系统产生引起钙网蛋白时空过表达的转基因小鼠。这些小鼠与Nkx2.5-Cre小鼠杂交，Nkx2.5-Cre小鼠在Nkx2.5启动子的控制下表达cre重组酶，Nkx2.5启动子是早期心脏发育所必需的转录因子。钙网蛋白过表达与6 ~ 10周龄PR间期、QRS间期延长、心动过缓、猝死有关。此外，一些NKx2.5-CRT转基因小鼠在7周龄时显示出明显的水肿。结论：钙网蛋白在心脏中的过度表达与HCN 1表达的降低有关，钙网蛋白在HCN 1基因调控中起重要作用。

项目成果

Improved assay for differential diagnosis between Pompe disease and acid alpha-glucosidase pseudodeficiency on dried blood spots.

改进了干血斑上庞贝病和酸性 α-葡萄糖苷酶假性缺乏症的鉴别诊断方法。

• 发表时间: 2011
• 期刊: Molecular Genetics and Metabolism
• 影响因子: 3.8
• 作者: Nakamura K;et all
• 通讯作者: et all

Novel mutations of GLA gene indentified in screening of Fabry disease.

法布里病筛查中发现的 GLA 基因新突变。

• 发表时间: 2008
• 作者: Hattori;et al.
• 通讯作者: et al.

Fabry病の疫学と診断

法布里病的流行病学和诊断

• 发表时间: 2010
• 期刊: 神経内科 73巻
• 作者: Sato;S.;Takahashi;S.;Asamoto;M.;Naiki;T.;Naiki-Ito;A.;Asai;K.;Shirai;T.;Yoshito Ishizaki;中村公俊
• 通讯作者: 中村公俊

Glycine regulates proliferation and differentiation ofsalivary-gland-derived progenitor cells.

甘氨酸调节唾液腺祖细胞的增殖和分化。

• 发表时间: 2009
• 期刊: Cell Tissue Res. 336
• 作者: Nakamura;et al.
• 通讯作者: et al.

Newborn Screening for Fabry Disease.

新生儿法布里病筛查。

• 发表时间: 2008
• 作者: Nakamura;et al.
• 通讯作者: et al.