Research Project
Grant-in-Aid for Scientific Research (C)
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
All 2008 2007 2006
All Journal Article (24 results) (of which Peer Reviewed: 11 results) Presentation (14 results) Book (6 results)
Ren Fail 30
Pages: 97-105
Am J Nephrol 28
Pages: 34-36
Am J Nephrol 27
Pages: 409-415
Perit Dial Int 28
Pages: 34-46
Am J Nephrol 24
Am J Hypertens 19
Pages: 282-285
Nephrol Dial Transplant 21
Pages: 1087-1088
Pages: 2337-2338
J Am Soc Nephrol 17
Pages: 686-696
Peritoneal Dialysis Intemational 26
Pages: 633-640
J Am Soc Nphrol 17
American Journal of Hypertension 19(3)
Nephrology Dialysis Transplantation 21(4)
Pages: 1087-1087
Nephrology Dialysis Transplantation 21(8)
PERITONEAL DIALYSIS INTERNATIONAL 26(6)
Annual Revivew 2006, 中外医学社,東京
Pages: 121-125
