Elucidation of the mechanism for the activation of transcription factors and gene response in the aorta of the Postprandial state of rata

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: NISHIO Yoshihiko Shiga University of Medical Science, Undergraduate School of Medicine, Associate professor (40281084)
• Project Period (FY): 2006 – 2007
• Keywords: Insulin / Transcription Factors / C / EBP / Inflammatory genes

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.

Research Products

• [Journal Article] Increased expression of CCAAT/enhancer binding protein-beta and -delta andmonocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats. (2007)
  • Author(s): Sato Y, Nishio Y, Sekine O, 他
  • Journal Title: Diabetologia 50 Pages: 481-489
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Pitavastatin restores vascular dysfunction in insulin-resistant state byinhibiting NAD(P)H oxidase activity and uncoupled endothelial nitric oxidesynthase-dependent superoxide production. (2007)
  • Author(s): Shinozaki K, Nishio Y, Ayajiki K, 他
  • Journal Title: J Cardiovasc Pharmacol 49 Pages: 122-130
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] RBMX is a novel hepatic transcriptional regulator of SREBP-lc gene response tohigh-fructose diet. (2007)
  • Author(s): Takemoto T, Nishio Y, Sekine O, 他
  • Journal Title: FEBS Lett 581 Pages: 218-222
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rat (2007)
  • Author(s): Sato, Y., Nishio, Y., Sekine, O., et. al.
  • Journal Title: Diabetologia 50 Pages: 481-489
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pitavastatin restores vascular dysfunction in insulin-resistant state byinhibiting NAD(P)H oxidase activity and uncoupled endothelial nitric oxidesynthase-dependent superoxide production (2007)
  • Author(s): Shinozaki, K., Nishio, Y., Ayajiki, K., et. al.
  • Journal Title: J Cardiovasc Pharmacol 49 Pages: 122-130
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] RBMX is a novel hepatic transcriptional regulator of SREBP-1c gene response tohigh-fructose diet (2007)
  • Author(s): Takemoto, T., Nishio, Y., Sekine, O., et. al.
  • Journal Title: FEBS Lett 581 Pages: 218-222
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcription factor activating enhancer-binding protein-2beta. A negative regulator of adiponectin gene expression. (2006)
  • Author(s): Ikeda K, Maegawa H, UgiS, 他
  • Journal Title: J Biol Chem 281 Pages: 31245-53
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Transcription factor activating enhancer-binding protein-2beta. A negative regulator of adiponectin gene expression (2006)
  • Author(s): Ikeda, K., Maegawa, H., Ugi, S., et. al.
  • Journal Title: J Biol Chem 281 Pages: 31245-53
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 2型糖尿病と動脈硬化 (2007)
  • Author(s): 西尾善彦
  • Organizer: 第22回日本糖尿病合併症学会(シンポジウム)
  • Place of Presentation: 筑波
  • Year and Date: 2007-10-27
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Increased Expression of CCAAT/Enhancer Binding Protein-β and-δ and Monocyte Chemoattractant Protein-1 Genes in Aort as from Hyperinsulinemic Rats. (2006)
  • Author(s): Sekine O, 他
  • Organizer: 66th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Increased Expression of CCAAT/Enhancer Binding Protein-β and -δ and Monocyte Chemoattractant Protein-1 Genes in Aortas from Hyperinsulinemic Rats (2006)
  • Author(s): Sekine, O., Nishio, Y., Sato, Y., et. al.
  • Organizer: 66th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 高インスリン血症と血管炎症 (2006)
  • Author(s): 西尾善彦
  • Organizer: 第21回日本糖尿病合併症学会(シンポジウム)
  • Place of Presentation: 弘前
  • Year and Date: 2006-10-07
  • Description: 「研究成果報告書概要(和文)」より