| Budget Amount *help |
¥3,580,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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.
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