Molecular pharmacological approach to elucidate direct actions of thyroid hormone on arterial blood vessels

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: National Institute of Health Sciences
• Principal Investigator: SATO Yoji National Institute of Health Sciences, Division of Cellular and Gene Therapy Products, Section Chief (40312285)
• Project Period (FY): 2006 – 2007
• Keywords: Thyroid Hormone / Calcification / Smooth Muscle / Artery

Research Abstract

We recently found that thyroid hormone (TH) has a protective effect against vascular calcification, at least partly by up-regulating matrix Gla protein gene (Mgp) in aortic smooth muscle. As transforming growth factor-beta (TGFbeta) is associated with osteogenesis, we hypothesized that, TH also regulates the expression of TGFbeta isoforms in vascular smooth muscle cells. To test this hypothesis, rat aortic smooth muscle cells (RAOSMCs), cultured in the nominally TH-free medium, were treated with 3', 3, 5-taiiodo-L-thyronine (T3) for 48 hours. Quantitative RT-PCRs indicated that 24-30pM free T3 selectively facilitated gene expression of TGFbeta3 in RAOSMCs by 2-fold. Rat aortic smooth muscle from methimazole-induced hypothyroid rats also showed a 50% decrease in the TGFbeta3 mRNA level, compared to euthyroid rats. Using GeneChip RGrU34A and Ingenuity Pathway Analysis, we further identified Den as a gene whose expression is negatively associated with both TGFbeta signaling and thyroid status in vivo. As Den encodes decorin, which functions as a promoter of intimal calcification, our findings suggest that the anti-calcification activity of TH is attributable not solely to its effect on Mgp gene, but also to those on several calcification-associated genes.

Research Products

• [Journal Article] Maternal vitamin A altered gene profiles and structural maturation of the rat ductus arteriosus. (2007)
  • Author(s): Yokoyama U^*, Sato Y^*(* equalcontribution), Akaike T, Ishida S, Sawada J, Nagao T, Quan H, Jin M, Iwamoto M, Yokota S, Ishikawa Y, Minamisawa S.
  • Journal Title: Physiological Genomics 31 Pages: 139-157
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Maternal vitamin A altered gene profiles and structural maturation of the rat ductus arteriosus. (2007)
  • Author(s): Yokoyama U, Sato Y(equal contribution), Akaike T, Ishida S, Sawada J, Nagao T, Quan H, Jin M, Iwamoto M, Yokota S, Ishikawa Y, Minamisawa S.
  • Journal Title: Physiological Genomics 31 Pages: 139-157
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 甲状腺ホルモンによる血管平滑筋石灰化関連遺伝子の制御 (2008)
  • Author(s): 柳野 紗智子、佐藤 光利、鈴木 和博、佐藤 陽治
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 20080326-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] (correspondence) ; Regulatory roles of thyroid hormones in expression of genes associated with vascular smooth muscle calcification (2008)
  • Author(s): Yanagino S, Satoh M, Suzuki K, Sato Y.
  • Organizer: The 128th Annual Meeting of the Pharmacutical Society of Japan
  • Place of Presentation: (Yokohama, Japan)
  • Year and Date: 20080326-28
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Thyroid hormone regulates genes associated with vascular smooth muscle calcification. (2008)
  • Author(s): Yanagino S, Satoh M, Suzuki K, Sato Y.
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20080317-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] (correspondence) ; Thyroid hormone regulates genes associated with vascular smooth muscle calcification. (2008)
  • Author(s): Yanagino S, Satoh M, Suzuki K, Sato Y.
  • Organizer: The 81st Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: (Yokohama, Japan)
  • Year and Date: 20080317-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 動脈血管平滑筋細胞における甲状腺ホルモンの生理的ターゲットとしてのTGFβ遺伝子 (2007)
  • Author(s): 柳野 紗智子、佐藤 光利、鈴木 和博、佐藤 陽治
  • Organizer: 第117回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-06
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] (correspondence) ; Thyroid hormone targets TGFbeta gene in arterial smooth muscle cells. (2007)
  • Author(s): Yanagino S, Satoh M, Suzuki K, Sato Y.
  • Organizer: The 117th Annual Meeting of the Kanto Area Section of the Japanese Pharmacological Society
  • Place of Presentation: (Tokyo, Japan)
  • Year and Date: 2007-10-06
  • Description: 「研究成果報告書概要(欧文)」より