| Project/Area Number |
08457286
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Niigata University |
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Principal Investigator |
SHIMIZU Fujio Niigata Univ.Sch.Med., Professor, 医学部, 教授 (40012728)
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| Co-Investigator(Kenkyū-buntansha) |
ORIKASA Michiaki Niigata Univ.College of Biomed.Technol., Associate Professor, 医療短期大学部, 助教授 (30185681)
NARITA Ichiei Niigata Univ.Sch.Med, , assistant, 医学部, 助手 (20272817)
KAWACHI Hiroshi Niigata Univ.Sch.Med.Associate professor, 医学部, 助教授 (60242400)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | monoclonal antibody / glomerulosclerosis / proteinuria / adhesivemolecule / cytokine / extracellular matrix / macrophage / マクロファージ / ACE阻害剤 |
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| Research Abstract |
I rreversible sclerotic renal lesions were induced in rats by an intravenous injection of 500 ug of anti-Thy-1.1 monoclonal antibody (mAb) 1-22-3to unilaterally nephrectomized rats. This modelis characterized by the sustained marked proteinuria with typical sclerotic lesions in glomeruli as well as in tubulointerstitium. These lesions were inhibited by adhesive molecules suppressants, complement inhibitors, anti-fibrotic agents, ACE inhibitors and Chinese traditional medicines. We have compared the kinetics of various parametersofirreversible to those in reversiblemodels, both of which were induced by an intravenous injection of mAb 1-22-3. In irreversible models TRPM3-positive activated macrophage and alpha -smoothe muscle actin-positive cells were demonstrated to infiltrate to interstitium, even in relatively early phase, suggesting the important roles playd by these tubulointerstitiallesionsin leading to irreversiblescleroticlesions. Angiotensin receptorantagonist prevented progression to endo-stage renal failure by suppressing the expression of TGF-beta and type I,III collagens at mRNA and protein levels, indicating that these factors are also important for irreversible progression of renal lesions.
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