Anti-atherosclerotic factors induced by Smad signaling in vascular cells

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University
• Principal Investigator: YOKOTE Koutaro Chiba University, Graduate School of Medicine, Associate professor (20312944)
• Project Period (FY): 2006 – 2007
• Keywords: Atherosclerosis / TGF-beta / macrophage / Smad3 / MCP-1 / inflammation

Research Abstract

Aim: To investigate the molecular basis of TGF-beta signaling involved in its anti-atherosclerotic effect.
Methods and Results: Double knockout mice for ApoE and Smad3, a major intracellular signaling molecule for TGF-beta, were generated, and subjected to in vivo and in vitro analyses. The double knockout mice developed significantly larger atheromatous lesions in the aorta compared with the control apoE knockout mice. The aortic lesions of double knockout mice were rich in macrophages, scarce in collagen deposition, and highly expressed monocyte chemoattractant protein-1 (MCP-1). Inhibitory effect of TGF-beta on MCP-1 gene expression was lost in the peritoneal macrophages derived from Smad3 knockout mice. The Smad3 knockout macrophages were also resistant to growth inhibitory effect of TGF beta.
Conclusion: Our results suggest that endogenous Smad3 in macrophage has inhibitory effects on progression of atherosclerosis via modulation of inflammatory gene expression and cell growth.

Research Products

• [Journal Article] Development and characterization of IL-21-producing CD4+Tcells. (2008)
  • Author(s): Suto A et. al.
  • Journal Title: J Exp Med (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Development and characterization of IL-21-producing CD4+ T cells (2008)
  • Author(s): Suto A, Kashiwakuma D, Kagami S, Hirose K, Watanabe N, Yokote K, Saito Y, Grusby MJ, Iwamoto I, Nakajima H.
  • Journal Title: J Exp Med (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of TGF-β/Smad3 signaling in response to vascular injury. (2006)
  • Author(s): Yokote K et. al.
  • Journal Title: Trends. Cardiovasc. Med. 16 Pages: 240-245
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Influence of C-peptide on Early Glomerular Changes in Diabetic Mice. (2006)
  • Author(s): Maezawa Y, Yokote K et. al.
  • Journal Title: Diabetes Metab. Res. Rev. 22 Pages: 313-322
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Role of TGF-β/Smad3 signaling in response to vascular injury (2006)
  • Author(s): Yokote, K, Kobayashi, K. and Saito, Y.
  • Journal Title: Trends. Cardiovasc. Med 16 Pages: 240-245
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Influence of C-peptide on Early Glomerular Changes in Diabetic Mice (2006)
  • Author(s): Maezawa, Y., Yokote, K., Sonezaki, K., Fujimoto, M., Kobayashi, K., Kawamura, H., Tokuyama, T., Takemoto, M., Ueda S, Kuwaki, T., Mori, S., Wahren, J., Saito, Y.
  • Journal Title: Diabetes Metab. Res. Rev 22 Pages: 313-322
  • Description: 「研究成果報告書概要(欧文)」より