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2001 Fiscal Year Final Research Report Summary

Basic approach for intervention of renal sclerosis by modulating apoptosis

Research Project

Project/Area Number 12670096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionTEIKYO UNIVERSITY

Principal Investigator

HISHIKAWA Keiichi  Teikyo University, Pharmacology, Associate Professor, 医学部, 助教授 (50255460)

Project Period (FY) 2000 – 2001
Keywordsapoptosis / micro array / CTGF / caspase
Research Abstract

Connective tissue growth factor (CTGF) is overexpressed in a variety of fibrotic disorders such as renal fibrosis and atherosclerosis. Fibrosis is a common final pathway of renal diseases of diverse etiology, including inflammation, hemodynamics, and metabolic injury. Mechanical strains such as stretch, shear stress and static pressure are possible regulatory elements in CTGF expression. In this study, we examined the ability of static pressure to modulate CTGF gene expression in cultured human mesangial cells. Low static pressure (40-80 mmHg) stimulated cell proliferation via a protein kinase C dependent pathway. In contrast high static pressure (100-180 mmHg) induced apoptosis in human mesangial cells. This effect was reversed by treatment with CTGF antisense oligonucleotide, but not with transforming growth factor β(TGF-β1) neutralizing antibody or protein kinase C inhibitor. High static pressure not only up-regulated the expression of CTGF, but also the expression of extracellular matrix proteins (collagen I and IV, laminin). This up-regulation of extracellular matrix proteins was also reversed by treatment with CTGF antisense oligonucleotide. As judged by mRNA expression of a total of 1100 genes including apoptosis associated genes using DNA microarray techniques, recombinant CTGF protein induced apoptosis by down-regulation of a number of anti-apoptotic genes. Overexpression of CTGF in mesangial cells by transient transfection had similar effects Taken together, these results suggest that high blood pressure up-regulates CTGF expression in mesangial cells. High levels of CTGF in turn enhance extracellular matrix production and induce apoptosis in mesangial cells, and may contribute to remodeling of mesangium and ultimately glomerulosclerosis.

  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Keiichi Hishikawa: "Connective tissue growth factor induces apoptosis via caspase3 in cultured human aortic smooth muscle cells"European Journal of Pharmacology. 392. 19-22 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菱川慶一: "Connective Tissue Growth Facto (CTGF)と血管"血管. 23. 35-44 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Keiichi Hishikawa: "Static Pressure Regulates connective Tissue Growth Factor Expression in Human Mesangial Cells"The Journal of Biological Chemistry. 276・20. 16797-16803 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hishikawa K.: "Connective tissue growth factor induces apoptosis via caspase 3 in cultured human aortic smooth muscle cells"Eur J. Pharmacol. 392. 19-22 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hishikawa K.: "Static pressure regulates connective tissue growth factor expression in human mesangial cells"J. Biol. Chem.. 276. 16797-16803 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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