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Transcription factoys in autoimmune thiroid disease : its relevance to pathophysiology and novel therapeutic strategy

Research Project

Project/Area Number 10671038
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

IKUYAMA Shoichiro  Medical Institute of Bioregulation, Kyushu Univ. Associate Professor, 生体防御医学研究所, 助教授 (20184393)

Co-Investigator(Kenkyū-buntansha) NAWATA Hajime  Kyushu Univ. Dept. of Bioregulatory Sciences & Medicine, Professor, 大学院・医学系研究院, 教授 (10038820)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsanti-inflammatory drug / free fatty acid / ADRP / autoimmunity / PPAR / TSH受容体 / 主要組織適合抗原 / 転写因子 / バセドウ病 / インターフェロン / 甲状腺
Research Abstract

In order to search new therapeutic strategies for autoimmune thyroid diseases, we have worked on adipose differentiation-related protein (ADRP), which was originally identified as an early marker of adipose cell differentiation program. This protein is ubiquitously expressed and is involved in lipid storage as well as long chain fatty acid uptake. Since free fatty acid could be a mediator of inflammatory response, we aimed to disclose the regulatory mechanism of the ADRP gene expression. In the present study, we disclosed that the mouse ADRP gene expression is regulated by PPARg. Thus, PPARg ligands, troglitazone, pioglitazone and 1 5 -deoxy-D12,14-prostaglandin J2, increased ADRP mRNA levels in NMuLi mouse liver cells and J774.1 mouse macrophages in vitro. This increase was completely inhibited by actinomycin D.On the contrary, PPARa ligands, fenofibrate and bezafibrate, failed to increase the mRNA levels. In order to delineate the promoter region responsible for this PPARg-induced stimulation, we cloned an approximately 2.8kb 5'-flanking region of the mouse ADRP gene, and constructed luciferase reporter plasmids for the assessment of promoter activity. All chimeric constructs containing the promoter region, when transfected into NMuLi cells, exhibited significant luciferase activity by comparison to a control plasmid. Troglitazone or troglitazone plus 9 -cis-RA significantly stimulated promoter activity expressed by the promoter containing a fragment of-2090bp or longer, but not -2005bp or shorter, indicating that the region between -2090 and -2006bp is responsible for the PPARg action. These results will facilitate understanding of the mechanism of PPARg action on ADRP expression. We are currently examining physiological significance of ADRP in thyrocytes and regulation of autoimmune thyroid diseases.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Adachi M, et al: "Androgen-insensitivity syndrome as a possible coactivator disease"N Engl J Med. 343. 856-862 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Adachi M, et al.: "Androgen-insensitivity syndrome as a possible coactivator disease."N Engl J Med. 343. 856-862 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Adachi M, et al: "Androgen-insensitivity sndrome as a possible coactivator disease"N Engl J Med. 343. 856-862 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohe K et al.: "Nicotinamide protentiates TSHR and MHC class II promoter activity in FRTL-5 cells"Mol Cell Endocrinol. 149. 141-151 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nawata H et al.: "Human Ad4BP/SF-1 and its related nuclear receptor"J Steroid Biochem Mol Biol. 69. 323-328 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 生山祥一郎、他: "下垂体腺腫における転写因子の発現と前葉細胞の分化について"ホルモンと臨床. 47(増刊). 50-56 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohe K. et al: "Nicotinamide poteitiates TSHR and MHC class II promoter activity in FRTL5 cells." Mol Cell Endocrinol. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikuyama S. et al: "Expression of an orphan nuclear receptor DAX-1 in human pituitary adenomas." Clin Endocrinol. 48. 647-654 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mu Y-M, et al: "Low level of gucocorticoid receptor mRNA in pituitary adenom as manifesting Cushing's disease with resistance to a high dose-dexamethasone suppression test" Clin Endocrinol. 49. 301-306 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikuyama S, et al (分担): "Molecular and Genetic Approaches to Diseases: Immunology, Hematology, Oncology" Kyushu University Press, 67-73 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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