1996 Fiscal Year Final Research Report Summary
Basic Studies on Gene Therapy for Glomerulonephritis
| Project/Area Number |
07671245
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Department of Medicine, Niigata University School of medicene |
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Principal Investigator |
NAKAGAWA Yoichi Department of Medicine, Niigata University School of medicene Associate Professor, 医学部附属病院, 講師 (80211415)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Alport syndrome / benign familial hemeturia / thin basement membrane disease / type IV collagen / protooncogene / transcriptional factors / Thy-1,1 nephrits / all-trans retinoic acid |
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| 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
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[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)
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