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Gene regulation of prosteins related to renal function

Research Project

Project/Area Number 09470236
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTohoku University

Principal Investigator

TAKEUCHI Kazuhisa  Tohoku University, Graduate School of Med., Research Associa, 大学院・医学系研究科, 助手 (40260426)

Co-Investigator(Kenkyū-buntansha) SUGAWARA Akira  Tohoku University, Graduate School of Med., Research Associa, 大学院・医学系研究科, 助手 (90270834)
ITOH Sadayoshi  Tohoku University, Graduate School of Med., Professor, 大学院・医学系研究科, 教授 (40271613)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1997: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsThromboxane / Na-Cl transporter / NRF2 / PPAR / HFH-3 / transgenic rat / renal function / gen regulation / アンジオテンシン / Naclトランスポーター / ステロイド / マクロファージ / 転写因子 / Nrf2 / PPARγ / トロンボキサン受容体 / トロンボキサン合成酵素 / サイトカイン / Naトランスポーター / ギテルマン症候群 / 動脈硬化 / Na-Cl トランスポーター / インターフェロン / レチノイン酸受容体 / 高血圧
Research Abstract

1) We have studied the transcription regulation of rat thromboxane synthase (TXS) gene by peroxisome proliferator-activated receptor γ (PPARγ) in Mφ. The transcription activity of cloned 5'-flanking region (1.6 kb) of rat TXS gene (5'FL-TXS) was examined by luciferase reporter gene assay. TXS mRNA levels and transcription activity of 5'FL-TXS were inhibited by PPARγ. Deletion analysis showed that the element responsible for the PPARγ effect was located in a region containing the NF-E2/AP-1 site (-98/-88), which was indicated to be bound by NF-E2 related factor 2 (Nrf2). Finally, a direct interaction between PPARγ and Nrf2 was confirmed by GST pull-down assay. In conclusion, the Nrf2-binding site (-98/-88) is the major promoter of 5'FL-TXS in Mφ, which can be suppressed by activated PPARγ via a protein-protein interaction with Nrf2.
2)Thiazide-sensitive Na-Cl cotransporter (TSC) is localized exclusively to the renal distal convoluted tubule (DCT) in kidney. We examined the molecular mechanism of this renal TSC expression localization. We generated transgenic rats harboring the transcription regulatory region of TSC fused upstream of the LacZ gene. Immunohistochemical analysis clearly showed that LacZ gene expression was co-localized to cortical distal tubules with TSC, indicating that the 5'FL/rTSC regulates the renal tubule-specific expression of TSC. Transcriptional activity of the rTSC gene was stimulated by overexpression of HFH-3, and electrophoretic mobility-shift assay showed a direct binding of in vitro synthesized HFH-3 to the HFH-3/rTSC. In conclusion, the transcription regulatory region of TSC gene confers the DCT-specific gene expression in the kidney. The DCT-specific transcription factor HFH-3 may be involved in the renal tubule-specific transcription of TSC gene.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (32 results)

All 2000 1999 1998 1997 Other

All Journal Article (10 results) Publications (22 results)

  • [Journal Article] Supphession of rat thromboxane synthase gene transcription by peroxisome proliferator activated-receptor (PPAR)-5 in macrophages via an interaction of NF-E2 related ractor2.2000

    • Author(s)
      Ikeda Y, その他
    • Journal Title

      J Biol Chem 275

      Pages: 33142-33150

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Suppression of rat thromboxane synthase gene transcription by peroxisome proliferator activated-receptor(PPAR)-γ in macrophages via an interaction of NF-E2 related factor 2.2000

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

      J Biol Chem 275

      Pages: 33142-33150

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The 5-HT2 receptor antagonist sarpoghelate rednces plasma and nrinary levels of thromboxane Az and impreves microalbnminurai in non-insulin dependent deabetes mellitus patients.1999

    • Author(s)
      Ogawa S, その他
    • Journal Title

      Clin Exp Physiol Pharmacol 26

      Pages: 461-464

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The 5-HT2 receptor antagonist sarpogrelate reduces plasma and urinary levels of thromboxane A2 and improves microalbuminurai in non-insulin dependent diabetes mellitus patients1999

    • Author(s)
      Ogawa S, et al.
    • Journal Title

      Clin Exp Physiol Pharmacol 26

      Pages: 461-464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Structure and function of the 5'-Hanking region rat thromboxane receptor gene.1998

    • Author(s)
      Takahashi N, その他
    • Journal Title

      Biochem Biophys.Res Comm 244

      Pages: 489-493

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Structure and function of the5'-flanking region of rat thromboxane receptor gene1998

    • Author(s)
      Takahashi N, et al.
    • Journal Title

      Biochem Biophys Res Comm 244

      Pages: 489-493

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Assignment of rat thromroxane sythase(Tbxas) to chromosome 4p21-22 by tluorescence in with hybridization1997

    • Author(s)
      Takeuchi K, その他
    • Journal Title

      Cytogenet Cell Genet 76

      Pages: 47-48

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Three cases of Gitelman's syndrome pussibly caused by different mutations in thiazide-sensitive Na-Cl corransporter.1997

    • Author(s)
      Takeuchi K, その他
    • Journal Title

      Intern Med 36

      Pages: 582-585

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Assignment of rat thromboxane synthase gene(Tbxas) to Chromosome 4q21-22 by fluorescence in situ hybridization.1997

    • Author(s)
      Takeuchi K, et al.
    • Journal Title

      Cytogenet Cell Genet 76

      Pages: 47-48

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Three cases of Gitelman's syndrome possibly caused by different mutations in thiazide-sensitive Na-Cl contransporter.1997

    • Author(s)
      Takeuchi K, et al.
    • Journal Title

      Intern Med 36

      Pages: 582-585

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ogawa S.,Takeuchi K. et al.: "The 5-HT_2 receptor antagonist sarpogrelate reduces plasma and urinary levels of thromboxane A2 and improves microalbuminurai in non-insuli dependent dibetes mellitus patients"Clin Exp Physiol Pharmacol. 26. 461-464 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda Y.,Takeuchi K.,Kato T.,Taniyama Y.,Sato K.,Sugawara A.,Ito S.: "Transcriptional supression of angiotensin AT1a receptor gene expression by interfreron-γ in vascular smooth muscle cells"Biochem Biophys Res Comm. 262. 494-498 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogawa S.,Takeuchi K.,Sugimura K.,Fukuda M.,Lee R.,Ito S.,Sato T.: "Bezafibrate reduces blood glucose in type-2 diabetes mellitus"Metabolism. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Taniyama Y.,Takeuchi K.,Sugawara A.,Ikeda Y.,Sato K.,Ito S.: "Loss of function by a mutation in thiazide-sensitive Na-Cl cotransporter found in Gitelman's syndrome"In: Control and Diseases of Sodium Dependent Transporter Proteins and Ion Channels. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Taniyama Y.,Takeuchi K.,Sugawara A.,Ikeda Y.,Ito S.: "Effect of steroid hormones on gene transcription of thiazide-sensitive Na-Cl cotransporter"In: Control and Diseases of Sodium Dependent Transporter Proteins and Ion Channels. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 竹内和久: "Peroxisome proliferator-acitvated receptor (PPAR) と動脈硬化"最新医学. 54. 139-143 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi N,Takeuchi K,et al.: "Structure and function of the 5'-flanking region of rat thromboxane receptor gene." Biochem Biophys Res Comm. 244. 489-493 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugawara A,Takeuchi K,et al.: "Characterization of mouse retinoid X receptor(RXR)-β gene promotor:negative regulation by tumor necrosis factor(TNF)-α." Endocrinology. 139. 3030-3033 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Surawara A,Takeuchi K,et al.: "Negative regulation of rat thromboxane receptor gene by 15-deoxy-delta12,14-PGJ_2 and troglotazone by activationg PPAR-γ in vascular smooth muscle cells" J Am Soc Nephrol. 9. 358A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniyama Y,Takeuchi K,et al.: "Functional expression of human thaizide-sensitive Na-Cl cotransporter in mammalian cells." J Am Soc Nephrol. 9. 146A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato T,Takeuchi K,et al.: "Transcriptional down regulation of vascular angiotensin AT1a receptor gene expression by interferon-γ." J Am Soc Neprhol. 9. 355A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogawa S,Takeuchi K,et al.: "5-HT_2 receptor blockade reduces thromboxane A_2 biosynthesis and improved microalbuminuria and peripheral blood flow in NIDDM patients." J Am Soc Nephrol. 9. 121A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 竹内和久: "病態高血圧学" メジカルレビュー, 41-56 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 竹内和久: "病態高血圧学" メジカルレビュー, 71-94 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeuchi K, Tsutsumi E, Abe T, Takahashi N, et al.: "Assignment of rat thromboxane synthase gene (Tbxas) to chromosome 4q21-q22 by fluorescence in situ hydridization" Cytogenet Cell Genet. 76. 47-48 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeuchi K, Kato T, Taniyama Y, Tsunoda K, et al.: "Three cases of Gitelams's syndrome possibly,caused by different mutations in thiazide-sensitive Na-Cl cotransporter" Intern Med. 36. 582-585 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutsumi E, Takeuchi K, Abe T, Takahashi N, et al.: "Rat thromboxane synthase : c DNA cloning and gene expression regulation in hydronephrotic kidney" Prostaglandins. 53. 423-431 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Endo Y, Arima S, Yaoita H, Omata K, Takeuchi K, et al.: "Function of angiotensin II type 2 receptor in the postglomerular efferent arteriole" Kidney Int. 52 (Suppl.63). S205-S207 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arima S, Endo Y, Yaoita H, Omata K, Takeuchi K, et al.: "Possible role of P450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type-2 receptor in the isolated microperfused rabbit Af-Art" J Clin Invest. 100. 2816-2823 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Welch WL, Peng B, Takeuchi K, Abe K, Wilcox CS.: "Salt loading enhances rat TxA2/PGH2 receptor expression and TGF response to U-46619" Am J Physiol. 273. F976-F983 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi N, Takeuchi N, Sugawara A, Taniyama Y, et al.: "Structure and function of the 5'-flanking region of rat thromboxane receptor gene" Biochem Biophys Res Commun. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugawara A, Uruno A, Nagata T, Taketo M, Takeuchi K, et al.: "Characterization of mouse retinoid X receptor (RXR)-Beta gene promotor : negative regulation by tumor necrosis factor (TNF)-Alpha" Endocrinology. (in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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