Cntribution of proteinases to the progression of glomerulosclerosis
| Project/Area Number |
11671050
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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 | JUNTENDO UNIVERSITY |
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Principal Investigator |
SHIRATO Isao Juntendo University, School of Medicine, Assoc. Prof., 医学部, 助教授 (70138238)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | glomerulosclerosis / glomerular epithelial cell / proteinase / immunohistochemistry / cell culture / growth factor / rat / mouse / カテプシンL |
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| Research Abstract |
The contribution of proteinase to the progression of glomerular diseases was investigated by immunohistochemistry of animal model of progressive glomerular disease and cultivation of differentiated podocyte cell line.
The immunohistochemical expression of cathepsin L and its intrinsic inhibitors in glomeruli was examined in rats with puromycin aminonucleoside (PAN) nephrosis which exhibits progressive glomerulosclerosis based on podocyte damage.
The positive immunostaining was detected in almost all podocytes at day 4 when proteinuria and pathological changes of the podocytes developed, followed by a reduction of intensity at day 8 when maximum proteinuria was reached and glomerular tuft adhesion started. Cathepsin L was again expressed intensely at days 28 and 56 in limited podocytes, the distribution and frequency of which were almost identical to those of podocytes with morphological damage. Cystatin b, an intracellular inhibitor of cathepsin L, was not detected in the podocytes and c
… More
ystatin C, an extracellular inhibitor of cathepsin L, was not coexpressed with the protease.
Then we analyzed secretion of proteinases from differentiated podocyte cell line into the culture medium after stimulation with bFGF, PDGF, and TGF-b1 using Western blotting and gelatin zymography. The secretion of procathepsin L, a precursor of cathepsin L, was enhanced by bFGF but not by TGF-b1. Increased secretion of the proteinase was not accompanied with the secretion of its extracellular inhibitor, cystatin C.The activity of metalloproteinases (MMP-2 and MMP-9) in the medium was increased by TGF-b1 but not by FGF-2. The increased activity of metalloproteinases was not associated with increased secretion of their inhibitor (TIMP-1). PDGF had no effect on the secretion of proteinases and their inhibitors
Thus it was suggested that under pathological conditions proteinases secreted from podocytes might contribute to podocyte damage, which is a critical process for the development and progression of tuft adhesion and sclerosis. Less
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Report
(3 results)
Research Products
(11 results)
