Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats
Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats
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DOI：
10.2353/ajpath.2007.060972
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发表时间：
2007-09-01
影响因子：
6
通讯作者：
Tsujimura, Tohru
中科院分区：
文献类型：
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作者：
Hamada, Tetsuhiro;Sato, Ayuko;Tsujimura, Tohru
为了评估抑瘤素M（osm）基因治疗在肝再生中的有用性，我们研究了OSM cDNA的引入是否增强了二甲基亚硝胺（DMN）损伤的大鼠肝脏的再生。将日本血凝病毒包膜中包裹的OSM cDNA重复注射到脾脏中，导致OSM蛋白在肝脏枯否细胞中独家表达，伴随着体重、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、天冬氨酸氨基转移酶和丙氨酸氨基转移酶）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。对DMN治疗前后的osm基因治疗的时间过程研究表明，这种治疗不仅有效地增强DMN损伤的肝细胞再生，而且有效地防止了随后用DMN治疗引起的肝细胞毒性。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。
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 enclosed in hemagglutinating virus of Japan envelope into the spleen resulted in the exclusive expression of OSM protein in Kupffer cells of the liver, which was 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 proliferation. The apoptosis of hepatocytes and fibrosis were suppressed by osm gene therapy. Time-course studies on osm gene therapy before 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 anti-apoptosis of hepatocytes and suggest that osm gene therapy is useful, as preventive and curative means, for the treatment of patients with liver damage.