A NEW THERAPEUTIC STRATEGY FOR PERITONEAL SCLEROSIS ; USE OF ANTISENSE OLIGONUCLEOTIDES (ODN) AGAINST HSP47 IN RAT CHLORHEXIDINE GLUCONATE MODEL
| Project/Area Number |
11671039
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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 | Nagasaki University |
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Principal Investigator |
OZONO Yoshiyuki University Hospital, School of Medicine, Nagasaki University Professor, 医学部・附属病院, 教授 (90213719)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Takashi University Hospital, School of Medicine, Nagasaki University Assistant Professor, 医学部・附属病院, 助教授 (90128207)
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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 |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | CAPD / HSP47 / peritoneal tissue / antisense ODN for HSP 47 / rat peritonear sclerosis model / HSP 47 / HSP47 / 腹膜硬化 / 線維化 |
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| Research Abstract |
Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD). HSP47, a collagen-specific molecular chaperon, is essential for biosynthesis and secretion of collagen molecules. In the previous study, we demonstrated an increased expression of HSP47 in sclerotic peritoneum from CAPD patients and rat experimental model, induced by peritoneal injection of chlorhexidine gluconate (CG)s. In the present study, the inhibitory effects of antisense ODNs against HSP47 on the progression of peritoneal sclerosis was determined. Peritoneal sclerosis was developed by daily intra peritoneal injection of CG for 14 days. Antisense or sense HSP47 ODN was given together with CG from day 8. Rats were killed at day 14 and peritoneal tissue was taken out. We examined the expression of HSP47 by immunohistochemistry. The expression of collagen III, alpha-smooth muscle actin and ED-1 was also examined. The expression of HSP47 and collagen III, alpha-smooth muscle actin was increased in the thickened submesothelial areas of CG-treated peritoneal specimens, while those expression and the number of ED-1 positive cells were significantly reduced in antisense-treated group compared with those in CG and sense-treated groups. The expression of HSP47, alpha-smooth muscle actin and collagen III was not different between CG and sense-treated groups. Our results indicate that an important role of HSP47 in collagen accumulation during peritoneal sclerosis. It is suggested that inhibition of HSP47 by antisense ODNs against HSP47 may be a new therapeutic strategy in CAPD patients with peritoneal sclerosis.
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Report
(3 results)
Research Products
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