| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/enhancer binding protein (C/EBP) -b and C/EBP-d and leads to the induction of monocyte chemoattractant protein-1 (MCP-1) gene expression in aortas.
Insulin at 10 nmol/l significantly stimulated the mRNA expressions of C/EBP-b C/EBP -d and MCP-1, depending on activation of phosphatidy linositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knock down of C/EBP-bwith siRNA abolished the insulin-induced mRNA expression of MCP-1. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt, a downstream molecule of PI3K, were also increased. The mRNA expressions of C/EBP-b, C/EBP-dand MCP-1 in the aortas from fructose-fed rats were significantly elevated, by 330, 300, and 300%, respectively, compared with those of control-fed rats. The induction of mRNA expression of MCP-1 in the aortas was significantly correlated with the mRNA expressions of C/EBPs in the aortas. Furthermore, ChIP assay showed elevated binding of C/EBP-b to the 5'-upstream region of MCP-1 gene in the aortas from fructose-fed rats.
These findings clearly indicate the role of C/EBPs in the mechanism of up-regulation of MCP-1, an inflammation-related protein, observed in hyperinsulinaemic state, which may initiate the process of atherosclerosis.
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