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Study on the pathogenesis and mechanism of the development of thyroid-associated ophthalmopathy

Research Project

Project/Area Number 17590971
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKurume University School of Medicine

Principal Investigator

HIROMATSU Yuji  Kurume University School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Professor, 医学部, 教授 (10201740)

Co-Investigator(Kenkyū-buntansha) MIYAKE Ikuyo  Kurume University School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Research assistant, 医学部, 助手 (50291828)
KAKU Hiroo  Kurume University School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Research assistant, 医学部, 助手 (50320239)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsGraves' disease / Graves' ophthalmopathy / polymorphism / NFKB / CTLA-4 / TSH receptor / Adipogenesis / Nicotinamide / NFκB / IL-18 / CD40 / ICAM-1 / pioglitazone
Research Abstract

We have studied the pathogenesis and mechanism of the development of ophthalmopathy in Graves' disease.
1) Susceptibility genes to thyroid-associated ophthalmmopathy (TAO)
There are much evidence that cytokines, immunomodulators, transcription factors play important roles in the development of TAO.
In association studies we have shown that the polymorphisms of the IL-18, ICAM-1 and NFkB1 genes were significantly associated with the development of ophthalmopathy. On the other hand, CTLA-4 gene and CD40 gene polymorphisms were associated with Graves' disease, but not with TAO.
2) TSH receptor expression on the orbital fibroblasts and its modulation by nicotinamide
A recent randomized controlled trail showed the usefulness of nicotinamide on TAO. We investigated the effect of nicotinamide on cultured orbital fibroblasts (preadipocytes) in adipogenesis and expressions of TSH receptor on the fibroblasts.
We confirmed the expression of TSH receptor on orbital fibroblasts derived from patients with TAO. Pioglitazone, a PPARγ agonist, induced adiopogenesis and the expression of TSH receptor mRNA. Nicotinamide did not affect the expression of TSH receptor mRNA, but suppressed the proliferation of the fibroblasts.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005

All Journal Article (32 results) Book (1 results)

  • [Journal Article] Interleukin-12B gene polymorphism does not confer susceptibility to Graves' ophthalmopathy in Japanese population.2006

    • Author(s)
      Hiromatsu Y, et al.
    • Journal Title

      Endocrine Journal 53

      Pages: 753-759

    • NAID

      10020612453

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lack of association of Interleukin-18 gene polymorphism with Graves' disease or Graves' ophthalmopathy2006

    • Author(s)
      Mukai T, et al.
    • Journal Title

      Thyroid 16

      Pages: 243-248

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.2006

    • Author(s)
      Hiromatsu Y, et al.
    • Journal Title

      Diabetic Medicine 23

      Pages: 211-215

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 特殊なバセドウ病 バセドウ病眼症 ステロイド治療2006

    • Author(s)
      広松雄治
    • Journal Title

      日本臨床 64

      Pages: 2279-2285

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] バセドウ病眼症に対する新しい考え方2006

    • Author(s)
      広松雄治
    • Journal Title

      ホルモンと治療 54

      Pages: 665-673

    • NAID

      10018071917

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] バセドウ病眼症2006

    • Author(s)
      広松雄治
    • Journal Title

      日本臨床 内分泌症候群(第2版) 別冊1巻5号

      Pages: 307-310

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 甲状腺機能低下症に伴うミオパチー2006

    • Author(s)
      三宅育代, 賀来寛雄, 広松雄治
    • Journal Title

      日本臨床 内分泌症候群(第2版) 別冊1巻5号

      Pages: 405-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interleukin-12B gene polymorphism does not confer susceptibility to Graves' ophthalmopathy in Japanese population.2006

    • Author(s)
      Hiromatsu Y, Fukutani T, Ichimura M, Mukai T, Kaku H, Miyake I, Yamada K.
    • Journal Title

      Endocrine J. 53(6)

      Pages: 753-9

    • NAID

      10020612453

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lack of association of Interleukin-18 gene polymorphism with Graves' disease or Graves' ophthalmopathy2006

    • Author(s)
      Mukai T, Hiromatsu Y, Ichimura M, Fukutani T, Kaku H, Miyake I, Shoji S, Bednarczuk T, Koda Y.
    • Journal Title

      Endocrine J. 53(6)

      Pages: 753-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.2006

    • Author(s)
      Hiromatsu Y, Mukai T, Kaku H, Miyake I, Ichimura M, Fukutani T, Nakayama H, Takata K, Imamura Y, Shoji S, Yamada K, Koda Y, Bednarczuk T.
    • Journal Title

      Diabetic Medicine 23

      Pages: 211-215

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Steroid therapy for Graves' ophthalmopathy2006

    • Author(s)
      Hiromatsu Y
    • Journal Title

      Nippon Rinsho. 64(12)

      Pages: 2279-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A new approach for Graves' ophthalmopathy2006

    • Author(s)
      Hiromatsu Y
    • Journal Title

      Hormone and Research 54(8)

      Pages: 665-673

    • NAID

      10018071917

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Graves' ophthalmopathy2006

    • Author(s)
      Hiromatsu Y
    • Journal Title

      Nippon Rinsho. Suppl 1

      Pages: 307-10

    • NAID

      40016024548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Myopathy with hypothyroidism2006

    • Author(s)
      Miyake I, Kaku H, Hiromatsu Y
    • Journal Title

      Nippon Rinsho. Suppl 1

      Pages: 405-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.2006

    • Author(s)
      Hiromatsu Y, Mukai T et al.
    • Journal Title

      Diabetic Medicine 23

      Pages: 211-2115

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lack of association of Interleukin-18 gene polymorphism with Graves' disease or Graves' ophthalmopathy.2006

    • Author(s)
      Mukai T, Hiromatsu Y, Ichimura M et al.
    • Journal Title

      Thyroid 16

      Pages: 243-248

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interleukin-12B gene polymorphism does not confer susceptibility to Graves' ophthalmopathy in Japanese population.2006

    • Author(s)
      Hiromatsu Y, fukutani T, Ichimura M et al.
    • Journal Title

      Edocrine J 53

      Pages: 753-759

    • NAID

      10020612453

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 【バセドウ病とその周辺疾患 基礎・臨床研究の最新動向】 特殊なバセドウ病 バセドウ病眼症の進展 ステロイド治療。2006

    • Author(s)
      広松雄治
    • Journal Title

      日本臨床 64巻12号

      Pages: 2279-2285

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 【甲状腺疾患の新しい考え方】 バセドウ病眼症に対する新しい考え方2006

    • Author(s)
      広松雄治
    • Journal Title

      ホルモンと臨床 54巻8号

      Pages: 665-673

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association of CD40 Gene Polymorphism (C-1T) with Susceptibility and Phenotype of Graves' Disease.2005

    • Author(s)
      Kurylowicz A, et al.
    • Journal Title

      Thyroid 15

      Pages: 1119-1124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A C/T polymorphism in the 5' untranslated region of the CD40 gene is associated with later onset of Graves' disease in Japanese.2005

    • Author(s)
      Mukai T, et al.
    • Journal Title

      Endocrine Journal 52

      Pages: 471-477

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] バセドウ病患者における抗GAD抗体2005

    • Author(s)
      広松雄治
    • Journal Title

      内分泌・糖尿病科 20

      Pages: 414-418

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] (内分泌疾患update) 甲状腺 Basedow病眼症の病因・診断・治療2005

    • Author(s)
      広松雄治
    • Journal Title

      医学のあゆみ 213巻・5号

      Pages: 355-359

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of CD40 Gene Polymorphism (C-1T) with Susceptibility and Phenotype of Graves' Disease.2005

    • Author(s)
      Kurylowicz A, Kula D, Ploski R, Skorka A, Jurecka-Lubieniecka B, Zebracka J, Steinhof-Radwanska K, Hasse-Lazar K, Hiromatsu Y, Jarzab B, Bednarczuk T.
    • Journal Title

      Thyroid. 15(10)

      Pages: 1119-24

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A C/T polymorphism in the 5' untranslated region of the CD40 gene is associated with later onset of Graves' disease in Japanese.2005

    • Author(s)
      Mukai T, Hiromatsu Y, Fukutani T, Ichimura M, Kaku H, Miyake I, Yamada K.
    • Journal Title

      Endocr J. 52(4)

      Pages: 471-7

    • NAID

      130004769949

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of anti-GAD antibody in Graves' ophthalmopathy2005

    • Author(s)
      Hiromatsu Y, Mukai T, Kaku H, Miyake I
    • Journal Title

      Endocrinology and Diabetes 20(4)

      Pages: 414-418

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pathology, diagnosis and treatment of Graves' ophthalmopathy2005

    • Author(s)
      Hiromatsu Y
    • Journal Title

      Igakunoayumi 213(5)

      Pages: 355-359

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Somatostatin analogs for treatment of Graves' ophthalmopathy2005

    • Author(s)
      Hiromatsu Y
    • Journal Title

      Evidences based medicine in endocrinology and metabolism(Abe K, Nishikawa T (eds))(Bunkoudou)

      Pages: 63-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A C/T polymorphism in the 5' untranslated region of the CD40 gene is associated with later onset of Graves' disease in Japanese.2005

    • Author(s)
      Mukai T, Hiromatsu Y, Fukutani T, Ichimura M, Kaku H, Miyake I, Yamada K.
    • Journal Title

      Endocr J 52(4)

      Pages: 471-477

    • NAID

      130004769949

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of CD40 Gene Polymorphism (C-1T) with Susceptibility and Phenotype of Graves' Disease.2005

    • Author(s)
      Kurylowicz A, Kula D, Ploski R, Skorka A, Jurecka-Lubieniecka B, Zebracka J, Steinhof-Radwanska K, Hasse-Lazar K, Hiromatsu Y, Jarzab B, Bednarczuk T.
    • Journal Title

      Thyroid 15(10)

      Pages: 1119-1124

    • Related Report
      2005 Annual Research Report
  • [Journal Article] バセドウ病患者における抗GAD抗体.2005

    • Author(s)
      広松雄治, 迎徳範, 賀来寛雄, 三宅育代
    • Journal Title

      内分泌・糖尿病科 20巻4号

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 【内分泌疾患UPDATE】甲状腺Basedow病眼症の病因・診断・治療2005

    • Author(s)
      広松雄治
    • Journal Title

      医学のあゆみ 213巻5号

      Pages: 355-359

    • Related Report
      2005 Annual Research Report
  • [Book] 臨床に直結する内分泌・代謝疾患治療のエビデンス2005

    • Author(s)
      広松雄治
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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