• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

MOLECULAR MECHANISM OF HUMAN RENIN AND C-MYC, GENES REGULATION THROUGH NUCLEAR RECEPTOR LXR

Research Project

Project/Area Number 15590983
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionYOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE

Principal Investigator

TAMURA Kouichi  YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, SECOND DEPARTMENT OF INTERNAL MEDICINE, ASSOCIATE PROFESSOR, 医学部附属病院, 講師 (40285143)

Co-Investigator(Kenkyū-buntansha) UMEMURA Satoshi  YOKOHAMA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL SCIENCE AND CARDIORENAL MEDICINE, CHAIRMAN & PROFESSOR CHAIRMAN, 医学研究科, 教授 (00128589)
Project Period (FY) 2003 – 2004
KeywordsRenin / Nuclear receptor / Liver X receptor alpha (LXRα) / Promoter / Transcriptional regulation / Cyclic AMP / Oxidized cholesterol / c-myc
Research Abstract

The cAMP-signaling pathway plays a crucial role in the regulation of the renin gene, but the mechanism involved remains poorly understood. We have focused our studies of renin gene regulation on the unique cAMP responsive element (huREN/CNRE, -135 to -107) in the human renin promoter. We have cloned a protein that binds to this unique CNRE and demonstrated that this protein is liver X receptor-α (LXRα), a transcriptional factor of the nuclear receptor family. Transient expression of LXRα in human renin-producing Calu-6 cells increased cAMP inducibility of human renin promoter. Similarly, LXRα-stably transfected Calu-6 cells exhibited increased cAMP inducibility of renin promoter as well as the endogenous renin gene. Site-directed mutation of huREN/CNRE, which disrupted LXRα binding, decreased cAMP-induced transcriptional activity of human renin promoter. Furthermore, we demonstrated that the binding of LXRa derived from human juxtaglomerular cells, the main production site of renin in the kidney, to the huREN/CNRE in vivo. These results suggest that LXRα plays an important role in the cAMP-mediated regulation of human renin gene transcription by binding to CNRE. In parallel experiments, we demonstrated that LXRα can also bind to the homologous CNRE in the c-myc promoter. cAMP promotes transcription through c-myc/CNRE : LXRa interaction in LXRα-transiently transfected cells and increases c-myc mRNA expression in stably transfected cells. Identification of LXRα as a novel cAMP responsive nuclear modulator of renin and c-myc expression not only has cardiovascular significance but may have generalized implication in the regulation of gene transcription.

  • Research Products

    (18 results)

All 2005 2004 2003

All Journal Article (17 results) Book (1 results)

  • [Journal Article] The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardio myocyte hypertrophy2005

    • Author(s)
      Tanaka, Y., Tamura, K., Koide, Y., Sakai, M., Tsurumi, Y., Noda, Y., Umemura, M., Ishigami, T., Uchino, K., Kimura, K., Horiuchi, M., Umemura, S.
    • Journal Title

      FEBS Lett. 579

      Pages: 1579-1586

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of Factors that Affect Short-Term Blood Pressure Variability in Patients with Chronic Renal Failure2005

    • Author(s)
      Sakai, M., Tamura, K., Tanaka, Y., Tsurumi, Y., Okano, Y., Koide, Y., Endoh, T., Matsushita, K., Kihara, M., Hirawa, N., Toya, Y., Tokita, Y., Ohnishi, T., Umemura, S.
    • Journal Title

      Clin Exp Hypertens. 27

      Pages: 139-147

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells2005

    • Author(s)
      Hashimoto, T., Kihara, M., Sato, K., Imai, N., Tanaka, Y., Sakai, M., Tamura, K., Hirawa, N., Toya, Y., Kitamura, H., Umemura, S.
    • Journal Title

      FEBS Lett. 579

      Pages: 281-284

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nuclear receptor LXRα is involved in cAMP-mediated human renin gene2004

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

      Mol Cell Endocrinol 224

      Pages: 11-20

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alterations in renal endothelial nitric oxide synthase expression by salt diet in angiotensin type-1a receptor gene knockout mice2004

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

      J Am Soc Nephrol 15

      Pages: 1756-1763

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II2004

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

      Nature Cell Biology 6

      Pages: 499-506

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression2004

    • Author(s)
      Tamura, K., Chen, Y.E., Tanaka, Y., Sakai, M., Tsurumi, Y., Koide, Y., Kihara, M., Pratt, R.E., Horiuchi, M., Umemura, S., Dzau, V.J.
    • Journal Title

      Mol Cell Endocrinol. 224

      Pages: 11-20

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alterations in renal endothelial nitric oxide synthase expression by salt diet in angiotensin type-1 a receptor gene-knockout mice2004

    • Author(s)
      Sato, K., Kihara, M., Hashimoto, T., Matsushita, K., Koide, Y., Tamura, K., Hirawa, N., Toya, Y., Fukamizu, A., Umemura, S.
    • Journal Title

      J Am Soc Nephrol. 15

      Pages: 1756-17663

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II2004

    • Author(s)
      Zou, Y., Akazawa, H., Qin, Y., Sano, M., Takano, H., Minamino, T., Makita, N., Iwanaga, K., Zhu, W., Kudoh, S., Toko, H., Tamura, K., Kihara, M., Nagai, T., Fukamizu, A., Umemura, S., Iiri, T., Fujita, T., Komuro, I.
    • Journal Title

      Nature Cell Biology 6

      Pages: 499-506

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The angiotensin II type I receptor-associated protein, ATRAP, is a transmembrane protein and a modulator of angiotensin II signaling.2003

    • Author(s)
      Lopez-Ilasaca M, et al.
    • Journal Title

      Mol Biol Cell 14

      Pages: 5038-5050

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Different induction of PKC isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats.2003

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

      Hypertens Res 26

      Pages: 421-426

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lipoxygenase products regulate nitric oxide and inducible nitric oxide synthase production in interleukin-1beta stimulated vascular smooth muscle cells.2003

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

      Hypertens Res 26

      Pages: 177-184

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lipoxygenase products regulate nitric oxide and inducible nitric oxide synthase production in interleukin-1 beta stimulated vascular smooth muscle cells2003

    • Author(s)
      Hashimoto, T., Kihara, M., Yokoyama, K., Fujita, T., Kobayashi, S., Matsushita, K., Tamura, K., Hirawa, N., Toya, Y., Umemura, S.
    • Journal Title

      Hypertens Res. 6

      Pages: 177-184

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A case of acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan2003

    • Author(s)
      Tamura, K., Umemura, M., Yano, H., Sakai, M., Sakurai, Y., Tsurumi, Y., Koide, Y., Usui, T., Yabana, M., Toya, Y., Tokita, Y., Umemura, S.
    • Journal Title

      Clin Exp Nephrol. 7

      Pages: 67-71

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Different induction of PKC isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats2003

    • Author(s)
      Koide, Y., Tamura, K., Suzuki, A., Kitamura, K., Yokoyama, K., Hashimoto, T., Hirawa, N., Kihara, M., Ohno, S., Umemura, S.
    • Journal Title

      Hypertens Res. 26

      Pages: 421-426

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular pathophysiology of renin-angiotensin system2003

    • Author(s)
      Tamura, K.
    • Journal Title

      Yokohama Med Bull. 50

      Pages: 1-14

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The angiotensin II type I receptor-associated protein, ATRAP, is a transmembrane protein and amodulator of angiotensin II signaling2003

    • Author(s)
      Lopez-liasaca, M., Liu, X., Tamura, K., Dzau, V.J.
    • Journal Title

      Moll Bloll Cell. 14

      Pages: 5038-5050

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] アンジオテンシノーゲン.第2章,レニン-アンギオテンシン系の分子生物学.The Renin-Angiotensin System.(堀内正嗣, 伊藤 裕, 竹内和久, 楽木宏美編)2003

    • Author(s)
      田村功一, 他
    • Total Pages
      55-62
    • Publisher
      メデイカルレビュー社(東京)
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi