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1997 Fiscal Year Final Research Report Summary

Molecular Analysis of Age-associated Nephropathy

Research Project

Project/Area Number 08671304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Women's Medical College

Principal Investigator

YUMURA Wako  Tokyo Women's Medical College, Internal Medicene, Associate Professor, 医学部, 助教授 (50075438)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Naoki  Tokyo Metropolitan Institute of Gerontology, Department of Molecular Pathology,, 分子病理, 研究部長 (00115940)
NITTA Kousaku  Tokyo Women's Medical College, Internal Medicene, Assistant Professor, 医学部, 助手 (50241071)
Project Period (FY) 1996 – 1997
Keywordsglomerulosclerosis / aging / fos / extracellular matrix / hyperglycemia / ラミニン
Research Abstract

The number of sclerotic glomeruli increases with age even in normal aduts without any signs of primary or secondary glomerular diseases. To understand the mechanism of this age related glomerulosclerosis, we focused on the DNA binding proteins from proto-oncogenes. We stained normal rat kidney tissues from various age (17,55, and 110 weeks) with antibodies against proto-oncogene products. As a result, expression of mesangial c-fos protein increased with age. To know whether the increase of mesangial c-fos protein may enhance the expression of extracellular matrix (ECM), two mesangial cell lines in which c-fos were expressed in a high levels were established. One was established from a c-fos transgenic mouse (c-fos TG), and the other was a rat mesangial cell line transfected with c-fos gene (c-fos TF). These call lines were stained with antibody reactive with c-fos protein, and the levels of nuclear c-fos protein were determined by confocal microscopy. When the cell lines were cultured in RPM1640 without FCS (10 mM glucose), the immunofluorescence intensity of nuclear c-fos protein in c-fosTG and c-fosTF were 0.52+0.06 and 0.49+0.07 respectively. These values were atatistically higher than that of appropriate controls. We then examined the ECM gene expressions. Of mRNAs tested, laminin B1 transcripts were elevated when they were cultured in ROM1640 without FCS.The levels of ECM mRNA expression were nearly the same as in a condition when these cells were exposed to high glucose (30mM glucose).
Conclusion : One of the DNA binding protein, c-fos protein, increase with age in mesangium. This may be one of the causes of ECM synthesis, which leads to glomerulosclerosis with ageing.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 新田 孝作: "糸球体内皮細胞とメサンギウム細胞の相互作用に対するerythropoietinの影響" 日腎会誌. 39. 777-782 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Uchida: "Regulated expression of endothelin converting enzymes in glomerular endothelial cells." Journal of American Society of Nophrology. 8. 580-585 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯村 和子: "ループス腎炎における血漿交換療法の有用性" 日本アフェレシス学会雑誌. 16. 372-378 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 本田 一穂: "SLEやクリオグロブリン血症などの免疫複合体病" 腎と透析. 43. 489-494 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W Yumura: "Effect of prednisolone therapy on serum concentrations of soluble interleukin-2 receptor in patients with IgA nephropathy." Clin.Exper.Nephrol. 1. 212-215 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 内田 啓子: "アレルギー性薬剤性間質性腎炎" 医学のあゆみ. 180. 66-69 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Keiko Uchida, Shinichi Uchida, Kosaku Nitta, Wako Yumura and Hiroshi Nihei: "Regulated expression of endothelin converthing enzymes in glomerular endothelial cells." Journal of American Society of Nephrology. 8. 580-585 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wako Yumura, Kousaku Nitta, Hiroyuki Ozu, Kyouko Natori, Yoko Eto, Akira Kwashima and Hiroshi Nihei: "Effect of prednisolone therapy on serum concentrations of soluble interleukin-2 receptor in patients with IgA nephropathy." Clin.Exper.Nephrol.1. 212-215 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Utsunomiya, Toshiyuki Imasawa, Aya Abe, Keita Hirano, Tetsuya Kawamura, Ryuji Nagasawa, Tetsuya Mitarai, Naoki Maruyama and Osamu Sakai: "Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin A nephropathy." Clinical and Experimental Nephrology. 1. 83-91 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ryuji Nagsawa, Kouichi Kanozawa, Tetsuya Mitarai, Masaki Inagaki and Naoki Maruyama: "Unique phosphorylation of vimentin filaments in glomerular epithelial cells in culture and in disease" Nephron. 77. 373-377 (1997)

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      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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