| Project/Area Number |
06454352
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
ORITA Yoshimasa Osaka Uiv.Sch.of Med, Professor., 医学部, 教授 (70028398)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Toshiki Osaka Uiv.Faculty of Health and Sports Sciences, Assistant Professor., 健康体育部, 助手
IMAI Enyu Osaka Uiv.Sch.of Med, Assistant Professor., 医学部, 助手 (00223305)
和田 晃 大阪大学, 医学部, 助手 (50252648)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | glomerulonephritis / renal biopsy / mesangial cells / phenotypic change / caldesmon |
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| Research Abstract |
Study on the human renal biopsy specimens
In 1994, we studied the expression of alpha smooth muscle actin (SMA) and myosin heavy chain embryonic type (SMemb) in renal biopsy specimens from patients with renal diseases of various origins. There was a positive association between histological changes and expression of SMA,but the association was not impressive in the case of SMemb. In 1995, we investigated the possible involvement of caldesmon (Cd) in the progression of chronic glomerular disease and in the process of phenotypic changes in mesangial cells in vivo, because caldesmon is known to involve in the phynotypic changes and in the progress of atherosclerosis in vascular smooth muscle cells. In 20 IgA nephropathy patients, expression of Cd and SMA was examined by immunohistochemistry, and the pathological findings and clinical parameters of the each case was compared with the expression of Cd and SMA.The expression of both Cd and SMA was found to be associated with the progression o
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f pathological changes in overall patients. Furthermore, there was an impressive case where a marked decrease in the staining of Cd in re-biopsy was associated with the clinical and histological improvement after 2 month therapy with predonisone, suggesting that Cd may serve as a marker of activity of the disease including the responsiveness to the steroid therapy.
Studies using rats
It is important to identify the factors involved in the phenotypic change of mesangial cells in vivo to establish a rationale for therapeutic strategies for glomerulosclerosis, however, this is not an easy task if only human biopsy specimens are used for analyzes. We used rat model for this purpose, and we found the following facts. 1)Introduction of renin and angiotensinogen genes into rat glomeruli caused glomerulosclerosis and phenotypic change of mesangial cells (published in BBRC). 2)Inhibition of transforming growth factor-beta1 expression by antisense oligonucleotides suppressed extracellular matrix accumulation in experimental glomerulonephrit (Kidney International, in press). These two findings confirm the pivotal roles of renin-angiotensin system and TGF-beta1 in the development of phenotypic change of mesangial cells and progression of glomerular sclerosis. Less
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