New therapeutic strategy against peritoneal sclerosis using gene-modified macrophages

使用基因修饰巨噬细胞对抗腹膜硬化的新治疗策略

基本信息

批准号：
18590893
负责人：
MIYAZAKI Masanobu
金额：
$ 2.45万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590893/
关键词：
peritoneal sclerosis macrophage cationized gelatin HGF

项目摘要

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

腹膜硬化是腹膜透析患者的严重并发症之一，它可以防止长期的腹膜透析治疗。但是，腹膜硬化的发病机理仍然未知。在病理检查中，在一些腹膜硬化症和实验性腹膜硬化模型的患者中观察到巨噬细胞的积累。在这项研究中，我们检查了巨噬细胞在腹膜硬化的发展过程中的重要作用，并尝试使用基因改性的巨噬细胞可以预防腹膜硬化的发展。众所周知，巨噬细胞通过粘合剂分子浸润到炎症的组织中，并知道ICAM-1是重要的粘合菌丝中的重要的粘合物。首先，我们使用ICAM-1（细胞内粘合分子）基因敲除小鼠研究了巨噬细胞在腹膜硬化过程中的作用。 com…在腹膜组织中几乎没有观察到巨噬细胞的野生型，ICAM-1基因敲除模型，并在腹膜组织中观察到巨噬细胞，并从结果中显着抑制了巨噬细胞，从结果中显着抑制，在增厚的质体组织中累积的巨噬细胞在腹膜硬化的发育中起着重要的作用。其次，使用甲状腺含量（HGF）基因的阳离子明胶（从京都大学的Yasuhiko Tabata教授那里赠予基因化的巨噬细胞（从Yasuhiko Tabata教授那里），该基因被称为抗纤维化因子。由于巨噬细胞具有吞噬活性，并且能够迁移到发炎的部位，因此我们油炸以利用巨噬细胞作为媒介物表达和传递HGF基因。 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.进一步的研究对于在腹膜透析患者中应用这种方法是预防和抑制腹膜硬化症的工具。较少的

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Japanese extraneal collaborated study group:Effects of icodextrin on glycemic and lipid profiles in diabetic patients undergoing peritoneal dialysis.

日本体外合作研究小组：艾考糊精对接受腹膜透析的糖尿病患者血糖和血脂的影响。

DOI：
发表时间：
2007
期刊：
Am J Nephrol 27
影响因子：
0
作者：
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
通讯作者：
Kawaguchi Y

Mizoribine induces remission of relapsed ANCA-associated renal vasculitis

米佐立宾诱导复发性 ANCA 相关肾血管炎的缓解