| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Cardiac ankyrin-repeated protein (CARP) was originally identified as a protein specifically expressed in cardiomyocytes, but has recently been found to be up-regulated in some muscle diseases including muscular dystrophy and myopathy, suggesting that CARP may be induced in some pathological conditions.
In this study, we immunohistochemically analyzed renal biopsy samples from patients with glomerular diseases and two individuals with normal kidney. We found that CARP was expressed in renal podocytes at a high level in crescentic glomerulonephritis (GN), diabetic nephropathy (DN), and lupus nephritis (LN), although it was not expressed in normal kidney. Interestingly, in LN, CARP expression tended to be induced in cases exhibiting nephrotic syndrome, but less so in cases without nephrotic syndrome, suggesting that CARP expression is correlated with the severity of proteinuria.
Then we analyzed the expression of CARP in podocytes of Balb/c mice that had been administrated with LPS or adria
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mycin. When LPS and adriamycin were injected to mice, CARP was induced in glomerular cells that co-express synaptopodin, a marker for podocyte, whereas CARP was not induced in mice injected with PBS. Thus, it is strongly suggested that CARP is really induced in podocytes in response to podocyte-injury. Rat glomerular parietal epithelial cell (PEC) underwent morphological changes and exhibited membrane ruffling after treatment with LPS and angiotensin II. Interestingly, phalloidin staining detected accumulation of F-actin in these areas of membrane ruffling When we treated with anagiotensin receptor blocker (ARB), morphological and distributional changes were partially blocked. On the other hand, we immunohistochemically analyzed the CARP-positive cells in urine frojm patients of GN. We could detect a small number of CARP-positive cells. Although we also tried to identify a monoclonal antibody against CARP, we have not identified it yet.
In conclusion, it is suggested that immunohistochemical evaluation of CARP in biopsy samples or urine from patients with LN may be useful for diagnosis of disease severity, and probably for prediction of outcome in LN-patients. Less
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