2005 Fiscal Year Final Research Report Summary
Peritoneal membrane regeneration in peritoneal sclerosis
| Project/Area Number |
16590789
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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 |
MIYAZAKI Masanobu Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (10246100)
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| Project Period (FY) |
2004 – 2005
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| Keywords | peritoneal dialysis / peritoneal sclerosis / HSP47 / RNA interference / mesothelial cells / peritoneal regeneration |
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| Research Abstract |
The main pathological features of peritoneal membrane from the patients with long PD therapy are accumulation of collagen and loss of mesothelial cells. These peritoneal alteration leads peritoneal membrane failure and is the biggest problem disturbing the longer-PD treatment more than 5-7 years. To maintain the longer PD treatment, peritoneal regeneration is an important issue. In the present study, we focused two points. One is inhibition of peritoneal sclerosis progression and other is regeneration of mesothelial cells. In the former, we tried to silence the gene of an essential molecular chaperon associated with collagen synthesis, heat shock protein 47 (HSP47). In order to inhibition of HSP47 expression, we used small interfering RNA (siRNA) combined with cationized gelatin microspheres (CGM) as vector. After three days of single injection of HSP47 siRNA with CGM to parietal peritoneum, experimental peritoneal sclerosis was made by chlorhexidine injection into peritoneal cavity. H
… More
SP47 siRNA significantly inhibited the progression of peritoneal sclerosis. Furthremore, biodegradable CGM containing HSP47 siRNA could continuously release siRNA over 21 days as a result of microsphere degradation. In the experiment of peritoneal regeneration, we examined the peritoneum after the fibrotic parietal peritoneum was stripped from abdominal wall in rats with chlorhexidine-induced experimental peritoneal sclerosis. Seven days after the stripping procedure, the peritoneum was covered with cells positive for cytokeratins and HBME-1, markers for mesothelial cells. Scanning electron microscopy also showed microvilli at the surface of the cells, which were main morphological feature of peritoneal mesothelial cells. Immunochemical analysis demonstrated the appearance of cells positive for vimentin, a marker of mesenchymal cells before the regeneration of mesothelial cells. In conclusion, HSP47 gene silencing by siRNA method combined with CGM was effective for the inhibition of progression of experimental peritoneal sclerosis and mesothelial cells had possibility of regeneration even on the fibrotic peritoneum. Less
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Research Products
(10 results)
