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

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，参与多种发育过程、细胞分化和功能的建立。我们已经显示了maf大家族在人和猪的发育胰腺中的表达谱（Pancreas 2006）。maf家族成员mafA是一个重要的胰岛素基因转录激活因子，它不仅调控胰岛的发育，而且还调控整个胰腺和脂肪组织的发育，形成葡萄糖和脂肪因子网络。我们报告称，通过RNA干扰技术抑制小鼠胰腺中mafA mRNA水平，除编码胰岛素和胰高血糖素的基因外，还下调了脂肪细胞因子基因的表达（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，我们研究了mafA mRNA在培养的脂肪细胞3 T3-L1中的表达，并通过siRNA技术改变其水平，分析了分化过程中形态学变化以及与脂肪形成和脂肪细胞因子相关的基因谱的变化。通过mafA抑制减弱细胞分化，并且在脂肪细胞的细胞质中没有观察到脂肪滴积累。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是一个关键的调节剂，并具有建立细胞分化和细胞功能的多潜能，参与葡萄糖和脂质代谢。

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.