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

Maf是一个转录因子蛋白家族，具有典型的bZip结构，是蛋白质二聚化和DNA结合的基序，据报道，它调节了几种不同的发育过程，细胞分化和功能的建立。我们已经展示了maf家族在人类和猪发育中的胰腺中的表达谱（胰腺2006）。maf大分子之一maa在胰腺p细胞中被发现是胰岛素基因转录的强反激活因子，然而，现在已经清楚的是，maf家族不仅调节胰岛的发育，还调节整个胰腺和脂肪组织的发育，从而建立了葡萄糖和脂肪因子网络。我们报道，通过RNA干扰技术抑制小鼠胰腺中mafA mRNA水平，可以下调脂肪细胞因子基因的表达，以及编码胰岛素和胰高血糖素的基因（BBRC 2007）。脂肪细胞高度参与胰岛素作用和葡萄糖代谢以及脂质代谢。为了探讨mafA在脂肪细胞中的作用，我们利用siRNA技术研究了培养的脂肪细胞3T3-L1细胞中mafA mRNA的表达，并对其表达水平进行了修饰，分析了其在分化过程中形态学变化以及与脂肪形成和脂肪因子相关的基因谱的变化。mafA抑制了细胞分化，脂肪细胞胞质中未见脂肪滴积聚。mafA siRNA干扰可抑制脂肪细胞分化所需的成脂基因mRNA的表达。因此，mafA是一种关键的调节因子，在细胞分化和细胞功能的建立中具有多种潜能，参与糖脂代谢。

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.