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The role of GSK-3 dependent transcriptional factor on glomerulo injury

Research Project

Project/Area Number 16590791
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

INOUE Takeaki  Kumamoto University, University Hospital, associate professor, 医学部附属病院, 講師 (90322312)

Co-Investigator(Kenkyū-buntansha) TOMITA Kimio  Kumamoto University, Graduate School of Medical Sciences, professor, 大学院・医学薬学研究部, 教授 (40114772)
NONOGUCHI Hiroshi  Kumamoto University, Graduate School of Medical Sciences, assistant professor, 大学院・医学薬学研究部, 助教授 (30218341)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsglycogen synthase kinase β / podocyte / tubules / streptozocin / diabetic rat / 糖尿病ラット / 上皮細胞 / 腎不全 / 糸球体腎炎
Research Abstract

Diabetes mellitus is one of main causes of ESRD in many countries. Insulin inhibits glycogen synthase kinase β (GSK3β) via the phosphorylation of ser-9, and Contributes to the stimulation of glycogen and protein synthase. Blunted regulation of GSK3β is linked to several pathological conditions, such as diabetes and Alzheimer's disease. However, the pathophysiological role of GSK3β in diabetic nephropathy is still unknown. In this study, distribution of GSK3β mRNA along the nephron of rat was investigated using microdissection and reverse transcription coupled real time PCR method. GSK3β mRNA expressed in all nephron segments. The mRNA was abundant in glomerulus and distal tubules. In proximal tubules, relative small amount of GSK3β mRNA was observed. Diabetic rat was prepared by streptozocin injection (60mg/kg) through the tail vein. 1 week after the injection, blood sugar was significantly increased in rats with streptozocin injection (415±37 mg/dl) compared with control rats (112±25m … More g/dl). Real time PCR showed that the GSK3β mRNA expression was increased by 82±17% in glomerulus and by 40±11% in proximal tubules in diabetic rat. In contrast, GSK3β mRNA did not change in distal tubules. Western blot analysis using the monoclonal antibody specific to rat GSK3β and P-ser9-GSK3β, phosphorylated inactive form of GSK3β was performed. Western blot analysis revealed that GSK3β was significantly increased by 50±8% in glomerulus of diabetic rat compared with control rat. This increase was sustained at least up to 3 weeks. On the other hand, P-ser-GSK3β protein did not change in diabetic rat. Immunohistochemical analysis was performed using anti-GSK3β monoclonal antibody. GSK3β expression was evident at the peripheral area of the capillary. Some of them was colocalized with podocin, a marker protein for podocyte. Majority of synaptopodin, another marker for podocyte, was colocalized with GSK3β, indicated the expression of GSK-3β in podocyte
Expression of GSK3β along the nephron was demonstrated and augmentations of GSK3β mRNA and active form of GSK3β protein has become evident in the glomerulus of diabetic rat. These data suggested that early increase of GSK3β expression in the glomeruli could play an important role for the pathogenesis of diabetic nephropathy. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004

All Journal Article (12 results)

  • [Journal Article] Long-term renoprotective effect of combination therapy with prostaglandin El and angiotensin-converting enzyme inhibitor in patients with chronic renal failure.2005

    • Author(s)
      Nakayama Y, Nonoguchi H, Inoue T, Tomita K. et al.
    • Journal Title

      Hypertens Res. 28

      Pages: 733-739

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential effects of hyperosmolality on Na-K-ATPase and vasopressin-dependent cAMP generation in the medullary thick ascending limb and outer medullary collecting duct.2005

    • Author(s)
      Sakuma Y, Nonoguchi H, Inoue T, Tomita K. et al.
    • Journal Title

      Hypertens Res. 28

      Pages: 671-679

    • NAID

      10016904692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential effects of hyperosmolality on Na-K-ATPase and vasopressin-dependent cAMP generation in the medullary thick ascending limb and outer medullary collecting duct.2005

    • Author(s)
      Sakuma Y., Nonoguchi H., Takayama M., Yang T., Terada Y., Inoue T., Nakayama Y., Kohda Y., Sasaki S., Tomita K
    • Journal Title

      Hypertens Res. 28(8)

      Pages: 671-679

    • NAID

      10016904692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Long-term renoprotective effect of combination therapy with prostaglandin E1 and angiotensin-converting enzyme inhibitor in patients with chronic renal failure.2005

    • Author(s)
      Nakayama Y., Nonoguchi H., Kiyama S., Kohda Y., Inoue T., Tomita K
    • Journal Title

      Hypertens Res. 28(9)

      Pages: 733-739

    • NAID

      10016904966

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Long-term renoprotective effect of combination therapy with prostaglandin E1 and angiotensin-converting enzyme inhibitor in patients with chronic renal failure.2005

    • Author(s)
      Nakayama Y., Nonoguchi H., Inoue T., Tomita K.et al.
    • Journal Title

      Hypertens Res. 28

      Pages: 733-739

    • NAID

      10016904966

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differential effects of hyperosmolality on Na-K-ATPase and vasopressin-dependent cAMP generation in the medullary thick ascending limb and outer medullary collecting duct.2005

    • Author(s)
      Sakuma Y., Nonoguchi H., Inoue T., Tomita K.et al.
    • Journal Title

      Hypertens Res. 28

      Pages: 671-679

    • NAID

      10016904692

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of aquaporin-2 by metabolic acidosis.2004

    • Author(s)
      Nonoguchi H, Inoue T, Tomita K. et al.
    • Journal Title

      Am J Physiol Cell Physiol. 287(3)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene regulation of renal-osmotic stress-induced Na-CL organic solute cotransporter.2004

    • Author(s)
      Baba T, Nonoguchi H, Inoue T, Tomita K
    • Journal Title

      Nephron Exp Nephrol 96(3)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene regulation of renal-osmotic stress-induced Na-CL organic solute cotransporter.2004

    • Author(s)
      Baba T., Nonoguchi H., Itoh K., Nakayama Y., Kohda Y, Inoue T., Tomita K
    • Journal Title

      Nephron Exp Nephrol. 96(3)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of aquaporin-2 by metabolic acidosis.2004

    • Author(s)
      Nonoguchi H., Inoue T., Mori T., Nakayama Y, Kohda Y, Tomita K
    • Journal Title

      Am J Physiol Cell Physiol. 287(3)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of aquaporin-2 by metabolic acidosis.2004

    • Author(s)
      Nonoguchi H.
    • Journal Title

      Am J Physiol Cell Physiol. 287(3)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene regulation of renal-osmotic stress-induced Na-Cl organic solute cotransporter2004

    • Author(s)
      Baba T.
    • Journal Title

      Nephron Exp Nephrol 96

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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