Study on pancreatic cell lineage of growth and differentiation in culture cells and tissue

培养细胞和组织中胰腺细胞谱系生长和分化的研究

• 批准号: 17591443
• 负责人: TSUCHIYA Mariko
• 金额: $ 2.29万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591443/
• 关键词: pancreatic cell; β cell; transcription factor; siRNA; adipocyte; adinocytokine; mafA; c-maf; mafB; insulin; transcription factor; インスリン; 発生 分化; β細胞; maf

Maf is a family of transcription factor proteins characterized by a typical bZip structure, a motif for protein dimerization and DNA binding, have been reported to be regulating several distinct developmental processes, cellular differentiation and establishment of function. We have shown the expression profiles of the large maf family in the developing pancreas of human and porcine(Pancreas 2006). One of the large maf molecules, mafA, has been found to be as a strong transactivator of insulin gene transcription in pancreatic p cells, however, it is now clear that the maf family not only regulate islet development but the development of the the entire pancreas and adipose tissue, resulting in the establishment of the glucose and adipokine network. We reported that suppression of the mafA mRNA level in the mouse pancreas by the RNA interference technique down-regulated expression of the adipocytokine genes in addition to the genes encoding insulin and glucagons(BBRC 2007). Adipocytes are highly involved in insulin action and glucose metabolism as well as in lipid metabolism. To explore the role of mafA in adipocytes, we investigated mafA mRNA expression and modified its level in cultured adipocytes, 3T3-L1 cells, by the siRNA technique, and analyzed the resulting alterations of morphological changes and the gene profile related to adipogenesis and adipocytokines during the differentiation. Cell differentiation was attenuated by mafA suppression, and no adipodroplet accumulation was observed in the cytoplasm of the adipocytes. mRNA expression of adipogenic genes which are essential genes for adipocyte differentiation, was suppressed by mafA siRNA interference. Thus, mafA is a key modulator and has multi-potentiality for establishing cell differentiation and cell function, that are involved in glucose and lipid metabolism.

MAF是一个转录因子家族，具有典型的bZip结构，是蛋白质二聚化和DNA结合的基序，已被报道调控着几个不同的发育过程、细胞分化和功能的建立。我们已经展示了大的maf家族在人和猪的发育中的胰腺中的表达谱(胰腺2006)。MAF大分子之一MafA被发现在胰腺p细胞中是胰岛素基因转录的强反式激活因子，然而，现在清楚的是，Maf家族不仅调节胰岛发育，而且调节整个胰腺和脂肪组织的发育，导致葡萄糖和脂肪因子网络的建立。我们报道，通过RNA干扰技术抑制小鼠胰腺中Mafa mRNA的水平，不仅下调了编码胰岛素和胰升糖素的基因，还下调了脂肪细胞因子基因的表达(BBRC2007)。脂肪细胞不仅参与脂肪代谢，还参与胰岛素作用和葡萄糖代谢。为了探讨Mafa在脂肪细胞中的作用，我们利用siRNA技术研究了Mafa在脂肪细胞3T3-L1细胞中的表达和水平，并分析了脂肪细胞分化过程中形态变化和与脂肪形成相关的基因表达谱的变化。Mafa抑制可抑制细胞分化，脂肪细胞胞浆内未见脂滴聚集。MafA siRNA干扰抑制了脂肪细胞分化所必需的成脂基因的mRNA表达。因此，MafA是一个关键的调节因子，在建立细胞分化和细胞功能方面具有多方面的潜力，而细胞分化和细胞功能与葡萄糖和脂肪代谢有关。

项目成果

Supression of mafA mRNA with siRNA attenuates Morphology and function of adipocyte differentiation by 3T3-L1 cells

用 siRNA 抑制 mafA mRNA 会减弱 3T3-L1 细胞脂肪细胞分化的形态和功能

• 发表时间: 2008
• 作者: Mariko;Tsuchiya;Atsushi;Maeda;Kazuki;Yasuda;Ken;Tsuchiya
• 通讯作者: Tsuchiya

In vivo suppression of mafA mRNA with siRNA and alteration of the gene expression profile, especially of adipocytokine genes, in mouse liver analyzed by the microarray method

通过微阵列方法分析小鼠肝脏中 siRNA 体内 mafA mRNA 的抑制以及基因表达谱的改变，尤其是脂肪细胞因子基因

• 发表时间: 2007
• 作者: Mariko;Tsuchiya;Atsushi;Maeda;Junko;Tanaka;Ken;Tsuchiya
• 通讯作者: Tsuchiya

Supression of mafs expression by the siRNA technique alters the geneprofile related to pancreatic endocrine hormone and adipocytokine in vivo and in vitro

siRNA技术抑制mafs表达改变了体内外与胰腺内分泌激素和脂肪细胞因子相关的基因谱

• 发表时间: 2007
• 作者: Mariko;Tsuchiya;Akiko;Hayashi;Junko;Tanaka;Atsushi;Maeda;Ken;Tsuchiya;Mariko Tsuchiya
• 通讯作者: Mariko Tsuchiya

Potential roles of large mafs in cell lineages and developing pancreas

• DOI: 10.1097/01.mpa.0000220867.64787.99
• 发表时间: 2006-05-01
• 期刊: PANCREAS
• 影响因子: 2.9
• 作者: Tsuchiya, Mariko;Taniguchi, Shigeki;Tsuchiya, Ken
• 通讯作者: Tsuchiya, Ken

In vivo suppression of mafA mRNA with siRNA and analysis of the resulting alteration of the gene expression profile in mouse pancreas by the microarray method

用 siRNA 体内抑制 mafA mRNA，并通过微阵列方法分析小鼠胰腺中基因表达谱的变化

• 发表时间: 2007
• 期刊: Biochemical Biophysical Research Communications 356
• 作者: M. Tsuchiya;T. Yoshid;S. Taniguchi;K. Yasuda;A. Maeda;A. Hayashi;K. Tsuchiya;et. al.
• 通讯作者: et. al.