New therapeutic strategy against peritoneal sclerosis using gene-modified macrophages
| Project/Area Number |
18590893
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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, Guest researcher (10246100)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Katsushige Nagasaki University, Graduate school of Biomedical Sciences, Assistant professor (40398144)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | peritoneal sclerosis / macrophage / cationized gelatin / HGF |
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| Research Abstract |
Peritoneal sclerosis is one of the serious complications among the patients with peritoneal dialysis and it prevents long-term peritoneal dialysis therapy. However, the pathogenesis of peritoneal sclerosis remains unknown. In pathological examination, accumulation of macrophages is observed in some patients with peritoneal sclerosis and experimental peritoneal sclerosis model. In this study, we examined an important role of macrophages during the development of peritoneal sclerosis and we tried whether the development of peritoneal sclerosis can be prevented using gene-modified macrophages.
It is well known that macrophages infiltrate into inflamed tissue via adhesion molecule and that ICAM-1 is known as one of important adhesion molecules in macrophage infiltration. Firstly, we studied a role of macrophages during the course of peritoneal sclerosis, using ICAM-1(intracellular adhesion molecule)knockout mice using experimental peritoneal sclerosis model with chlorhexidine gluconate. Com
… More
paring with wild type, ICAM-1 knockout model, macrophage was hardly observed in peritoneal tissue and submesothelial tissue thickening was significantly suppressed From the results, accumulated macrophages in thickened submesothelial tissue plays an important role in development of peritoneal sclerosis.
Secondly, gene-modified macrophages were made using cationized gelatin(kindly gifted from Professor Yasuhiko Tabata in Kyoto University) with hepatic growth factor(HGF) gene, which is known to work as antifibrotic factor. We fried to utilize macrophages as a vehicle to express and deliver HGF gene at the peritoneum because macrophages have phagocytotic activity and are capable of migrating to inflamed sites. Intravenous transfer of macrophages carrying HGF expression vector significantly suppressed the submesothelial thickening and reduced collagen III expression in chlorhexidine treated mice.
In conclusion, macrophages have a central role of pathogenesis of peritoneal sclerosis and gene-modified macrophages with cationized gelatin including HGF gene may open a new therapeutic strategy against peritoneal sclerosis. Further studies are necessary for applying this method in the patients with peritoneal dialysis as tool of preventing and inhibiting peritoneal sclerosis. Less
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Report
(3 results)
Research Products
(44 results)
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[Journal Article] Regression of peritoneal mesothelium in a rat model of peritoneal fibrosis2008
Author(s)
Nishioka, Y., Miyazaki, M., Abe, K., Furusu, A., Harada, T., Ozono, Y., Taguchi, T., Koji, T., Kohno, S
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Journal Title
Ren Fail 30
Pages: 97-105
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Japanese extraneal collaborated study group:Effects of icodextrin on glycemic and hpid profiles in diabetic patients undergoing peritoneal dialysis2007
Author(s)
Babazon T, Nakamoto H, Kasai K, Kuriyama S, Sugimoto T, Nakayama M, Hamada T, Furuya R, Hasegawa H, Kasahara M, Moriishi M, Miyazaki M, Sato M, Yorioka N, Kawaguchi Y
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Journal Title
Am J Nephrol 27
Pages: 409-415
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Gene transfer using nonviral delivery systems2007
Author(s)
Miyazaki, M., Obata, Y., Abe, K., Furusu, A., Koji, T., Tabata, Y., Kohno, S
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Journal Title
Perit Dial Int 28
Pages: 34-46
Description
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[Journal Article] Suppression of renal tubulointerstitial fibrosis by small interfering RNA targeting heat shock protein 472007
Author(s)
Xia, Z., Abe, K., Furusu, A., Miyazaki, M., Obata, Y., Tabata, Y., Koji, T., Kohno, S
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Journal Title
Am J Nephrol 28
Pages: 34-46
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Japanese extraneal collaborated study group : Effects of icodextrin on glycemic and lipid profiles in diabetic patients undergoing peritoneal dialysis2007
Author(s)
Babazono, T., Nakamoto, H., Kasai, K., Kuriyama, S., Sugimoto, T., Nakayama, M., Hamadam, T., Furuya, R., Hasegawa, H., Kasahara, M., Moriishi, M., Miyazaki, M., Sato, M., Yorioka, N., Kawaguchi, Y
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Journal Title
Am J Nephrol 24
Pages: 409-415
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Japanese extraneal collaborated study group:Effects of icodextrin on glycemic and lipid profiles in diabetic patients undergoing peritoneal dialysis.2007
Author(s)
Babazono T, Nakamoto H, Kasai K, Kuriyama S, Suginoto T, Nakayama M, Hamada T, Furuya R, Hasegawa H, Kasahara M, Moriishi M, Miyazaki M, Sato M, Yorioka N, Kawaguchi Y
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Journal Title
Am J Nephrol 27
Pages: 409-415
Related Report
Peer Reviewed
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[Journal Article] Renal circulatory effects of acetazolamide in patients with essential hypertension2006
Author(s)
Horita, Y., Yakabe, K., Tadokoro, M., Suyama, N., Hayashida, K., Kawano, Y., Miyazaki, M., Kohno, S., Taura, K
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Journal Title
Am J Hypertens 19
Pages: 282-285
Description
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[Journal Article] Mizoribine induces remission of relapsed ANCA-associated renal vasculitis2006
Author(s)
Nishioka, Y., Horita, Y., Tadokoro, M., Taura, K., Suyama, N., Miyazaki, M., Harada, T., Kohno, S
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Journal Title
Nephrol Dial Transplant 21
Pages: 1087-1088
Description
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[Journal Article] Changing mizoribine administration from three divided doses to one single dose induced remission of relapsed membranous nephropathy2006
Author(s)
Nishioka, Y., Horita, Y., Tadokoro, M., Taura, K., Suyama, N., Miyazaki, M., Harada, T., Kohno, S
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Journal Title
Nephrol Dial Transplant 21
Pages: 2337-2338
Description
「研究成果報告書概要(欧文)」より
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