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1996 Fiscal Year Final Research Report Summary

Basic Studies on Gene Therapy for Glomerulonephritis

Research Project

Project/Area Number 07671245
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionDepartment of Medicine, Niigata University School of medicene

Principal Investigator

NAKAGAWA Yoichi  Department of Medicine, Niigata University School of medicene Associate Professor, 医学部附属病院, 講師 (80211415)

Co-Investigator(Kenkyū-buntansha) NARITA Ichiei  Clinical and Research Associate, 医学部, 助手 (20272817)
UENO Mituhiro  Clinical and Research Associate, 医学部・附属病院, 助手 (90260546)
NISHI Shinichi  Clinical and Research Associate, 医学部・附属病院, 助手 (70251808)
Project Period (FY) 1995 – 1996
KeywordsAlport syndrome / benign familial hemeturia / thin basement membrane disease / type IV collagen / protooncogene / transcriptional factors / Thy-1,1 nephrits / all-trans retinoic acid
Research Abstract

1) Genetic analysis of hereditary renal diseases
We have analyzed the genomic DNA from Alport syndrome patients, which is characterized by specific morphological changes of glomerular basement membrane such as basket weave appearance. We have identified the deletion of type IV collagen alpha 5 chain from 3 patients. Two cases had partial deletion and another was supposed to have complete deletion of the alpha 5 and alpha 6 chains.
Benign familial hematuria is also known as thin basement membrane disease (TBMD) and characterized by diffuse thinning of lamina densa of the glomerular basement membrane. We have performed the genetic linkage analysis between type IV collagen alpha 3 or alpha 4 chain and TBMD.But there was no linkage, suggesting the genes responsible for TBMD were other than these basement membrane collagens.
2) Transcriptional factors in rat experimental glomerulonephritis
We have focused on protooncogenes such as c-fos, c-jun and c-myc, and AP-1 which is heterodimer complex of … More c-Fos and c-Jun, in rat anti Thy 1,1 nephritis and streptozotocin diabetic rats.
mRNA expression for c-myc was maximal at 4 or 5 days after the induction anti Thy 1,1 nephritis, which phase is cosistent with mesangial cell proliferation. AP-1 complex expressed srtrongly in the chronic, glomeruloscrelotic phase of STZ diabetic rats rather than just after the induction of the diabetes. These results reveald that these transcriptional factors play an important roles in mesangial proliferative glomerulonephritis, especially in the progressive and chronic phase of the disease.
3) Effects of all trans retinoic acid (ATRA) on mesangial cells
ATRA is known as an inducer of cell differentiation. This may suggests that ATRA induces growth suppression of mesangial cells via the induction of phenotypic change of the cells.
We have analyzed the effects of ATRA on cultured mesangial cells. ATRA suppressed the mesangial cell growth and mRNA expressions for c-fos, c-jun and c-myc. Then we administerd ATRA torats of anti Thy 1,1 nephritis. Mesangial cell number and matix score were significantly suppressed in ATRA treated rats. These results strongly suggested that the down regulation of these transcriptional factors could be a possible candidate for the treatment of mesangial proliferative glomerulonephritis. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 竹田徹朗,中川洋一他: "腎疾患患者の遺伝子解析の現状" Medical Practice. 13. 245-247 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Yamazaki et al.: "Two Brothers with p^<47>-phox deficient chrouic granulomatous disecse associated with end-stage veual failurl" Nephrol Dial Transplant. 10. 2334-2336 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山崎 肇,中川洋一他: "アルポート症候群と良性家族性血尿" 感染・炎症・免疫. 25. 46-49 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山崎 肇,中川洋一他: "アルポート症候群と良性家族性血尿" 最新医学. 50. 1958-1964 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Yamazaki et al: "No linkage to the COL4 A4 gene locus in Japanese thin basement membrane disease family" Nephrology. 1. 315-321 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Sakatsume et al.: "Mesangial Cell-Matrix Iuteractions : Modulation of matrix expression in mesangial cells by extracellular matrices" Exp. Nephrol. 3. 362-368 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuro Takeda, Hajime Yamazaki, Akihiko Saito, Yoichi Nakagawa, and Masaaki Arakawa: "Present Status of Genetic Analysis of Renal Diseases." Medical Practice. 13(2). 245-247 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yamazaki, S.Nishi, T.Chou, Y.Nakagawa, H.Shimada, H.Nunoi, S.Imajoh-Ohmi, K,Yoshioka and M.Arakawa: "Two brothers with p47-phox-deficient chronic granulomatous disease associated with end-stage renal fairule." Nephrol Dial Treansplant. 10. 2334-2336 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yamazaki, Akihiko Saito, Yoichi Nakagawa, Shinichi Nishi, and Masaaki Arakawa: "Alport syndrome and Benign familial hematuria" Infection, Inflammation and Immunity. 25(1). 46-49 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yamazaki, Akihiko Saito, Yoichi Nakagawa, and Masaaki Arakawa: "Alport syndrome and Benign familial hematuria" Saishin Igaku. 50(10). 1958-1964 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hajime Yamazaki, Yoichi Nakagawa, Akihiko Saito, Shin-ichi Nishi, Minoru Sakatsume, tetsuro Takeda, Yuichiro Maruyama, Sojiro Ogino, Shiro Maruyama, Toshio Mochizuki, Stephen T Reeders and Masaaki Arakawa: "No linkage to the COL4A3 gene locus in Japanese thin basement membrane disease families." Nephrology. 1. 315-321 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minoru Sakatsume, Akihiko Saito, Tetsuro Takeda, Hajime Yamazaki, Ichiei Narita, Shin-ichi Nishi, Yoichi Nakagawa and Masaaki Arakawa: "Mesangial cell-matrix interactions : Modulation of matrix expression in mesangial cells by extracellular matrices." Exp.Nephrol.3. 362-368 (1995)

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

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Published: 1999-03-09  

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