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Study on the differentiation of oval cells for the development of liver-targeted regenerative medicine

卵圆细胞分化研究，发展肝脏靶向再生医学

基本信息

批准号：
17590363
负责人：
TSUJIMURA Tohru
金额：
$ 2.3万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590363/
关键词：
liver regeneration gene theraphy oncostatin M hepatoma-derived growth factor oval cells 肝幹細胞肝再生医療 Ws Wsラット microarray シグナルシークエンストラップ法

项目摘要

Oval cells of the liver participate in liver regeneration when hepatocytes are prevented from proliferating in response to liver damage. To clarify the role of hepatoma-derived growth factor (HDGF) in the liver regeneration involving oval cells, we examined the expression of HDGFmRNA in the liver undergoing regeneration in the 2-acetylaminofluorene/partial hepatectomy model. Expression levels of HDGFmRNA changed in correlation to the number of oval cells, and its expression was exclusively observed in oval cells. These results suggest that HDGF may play an important role in the proliferation of oval cells, thereby promoting liver regeneration.To assess the usefulness of Oncostatin M (osm) gene therapy in liver regeneration, we examined whether the introduction of osm cDNA enhances the regeneration of livers damaged by dimethylnitrosamine (DMN) in rats. Repeated injection of osm cDNA in hemagglutinating virus of Japan envelope into the spleen resulted in the exclusive expression of OSM … More protein in Kupffer cells of the liver, which accompanied by increases in body weight, liver weight, and serum albumin levels and the reduction of serum liver injury parameters (bilirubin, aspartate aminotransferase, and alanine aminotransferase) and a serum fibrosis parameter (hyaluronic acid). Histological examination showed that osm gene therapy reduced centrilobular necrosis and inflammatory cell infiltration and augmented hepatocyte proliferaion. The apoptosis of hepatocytes and the fibrosis were suppressed by osm gene therapy. Time-course studies on osm gene therapy prior to or after DMN treatment showed that this therapy was effective not only in enhancing regeneration of hepatocytes damaged by DMN but in preventing hepatic cytotoxicity caused by subsequent treatment with DMN. These results indicate that OSM is a key mediator for proliferation and antiapoptosis of hepatocytes and suggest that osm gene therapy is useful, as preventive and curative means, for the treatment of patients with liver damage. Less

当肝细胞响应于肝损伤而被阻止增殖时，肝的卵圆细胞参与肝再生。为了阐明肝癌衍生生长因子（HDGF）在涉及卵圆细胞的肝再生中的作用，我们检测了HDGFmRNA在2-乙酰氨基芴/部分肝切除模型中进行再生的肝中的表达。HDGFmRNA表达水平的变化与卵圆细胞的数量相关，其表达仅见于卵圆细胞。这些结果表明，HDGF可能在卵圆细胞的增殖中发挥重要作用，从而促进肝regeneration.To评估的有用性Oncostatin M（osm）基因治疗在肝regeneration. To，我们研究了是否引入osm cDNA增强二甲基亚硝胺（DMN）损伤的大鼠肝脏的再生。将日本血凝病毒囊膜中的osm cDNA重复注射到脾脏中，导致OSM的专一性表达 ...更多信息肝脏枯否细胞中的蛋白质，其伴随体重、肝脏重量和血清白蛋白水平的增加以及血清肝损伤参数（胆红素、天冬氨酸转氨酶和丙氨酸转氨酶）和血清纤维化参数（透明质酸）的降低。组织学检查显示，osm基因治疗可减少小叶中心坏死和炎性细胞浸润，促进肝细胞增殖。osm基因治疗可抑制肝细胞凋亡和肝纤维化。在DMN治疗之前或之后对osm基因治疗的时间过程研究表明，这种治疗不仅在增强DMN损伤的肝细胞再生方面有效，而且在预防随后用DMN治疗引起的肝细胞毒性方面有效。这些结果表明OSM是肝细胞增殖和抗凋亡的关键介质，并表明OSM基因治疗是有用的，作为预防和治疗手段，用于治疗肝损伤患者。少