Involvement of osteoactivin in inflammatory hepatocarcinogenesis: analysis of mice lacking osteoacitivin expression

骨激活素参与炎症性肝癌发生：缺乏骨激活素表达的小鼠的分析

• 批准号: 22590742
• 负责人: IDO Akio
• 金额: $ 3万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590742/
• 关键词: オステオアクチビン; 肝障害; 肝発癌; 肝再生; マクロファージ; 炎症性発癌; 四塩化炭素; 自然免疫; 貪食

In this study, we investigated an involvement of osteoacitivin, which is expressed in infiltrating macrophages, in repair of injured livers and hepatocarcinogenesis. In mice with CCl4-induced liver injury, osteoactivin was expressed in macrophages infiltrating in injured livers during repair process, and macrophages positive for osteoactivin exhibited enhanced ability of phagocytosis. When macrophages were depleted, repair of injured livers was suppressed. Additionally, mice lacking osteoactivin expression showed inhibition of both fibrosis and its resolution. When hepatoma cells were inoculated, following induction of liver injury, enhanced development of hepatic tumors was observed. These results suggest that osteoactivin play an important role in repair of injured livers and also in development of hepatocellular carcinoma occurring in the context of liver injury.

在这项研究中，我们研究了骨活性素在浸润性巨噬细胞中表达，参与损伤肝脏的修复和肝癌的发生。在ccl4诱导的小鼠肝损伤中，骨激活素在修复过程中浸润于损伤肝脏的巨噬细胞中表达，骨激活素阳性的巨噬细胞表现出增强的吞噬能力。当巨噬细胞被耗尽时，损伤肝脏的修复受到抑制。此外，缺乏骨激活素表达的小鼠显示纤维化及其消退受到抑制。当肝癌细胞接种后，在肝损伤诱导下，观察到肝肿瘤的发展增强。这些结果表明，骨激活素在损伤肝的修复和肝细胞癌的发展中起重要作用。

项目成果

肝障害の修復期に浸潤する肝マクロファージの欠損は肝障害を遷延化させる

肝损伤修复阶段浸润的肝巨噬细胞的缺乏会延长肝损伤

• 发表时间: 2012
• 作者: 熊谷公太郎;井戸章雄;椨 一晃;大野香織;小田耕平;最勝寺晶子;今中 大;馬渡誠一;呉 建;玉井 努;森内昭博;宇都浩文;桶谷眞;坪内博仁
• 通讯作者: 坪内博仁

Changing etiologies and outcomes of acute liver failure: a perspective from Japan

急性肝衰竭的病因和结果的变化：日本的视角

• DOI: 10.1111/j.1440-1746.2010.06574.x
• 发表时间: 2011
• 期刊: J Gastroenterology Hepatol
• 作者: Oketani M;Ido A;Tsubouchi H
• 通讯作者: Tsubouchi H

肝炎進展に伴い発現するオステオアクチビンは肝マクロファージの貪食に関与する

随着肝炎进展而表达的骨激活素参与肝脏巨噬细胞的吞噬作用。

• 发表时间: 2011
• 作者: 熊谷公太郎;井戸章雄;呉建;椨一晃;大野香織;小田耕平;最勝寺晶子;今中大;馬渡誠一;玉井努;森内昭博;宇都浩文;桶谷眞;坪内博仁
• 通讯作者: 坪内博仁

Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compaired to dietary fat

膳食果糖与膳食脂肪诱导的脂肪肝引起的大鼠部分肝切除术后的肝再生受损更严重

• 发表时间: 2011
• 期刊: Biochem Biophys Res Commun
• 作者: Tanoue S Uto H;Kumamoto R;Arima S;Hashimoto S;Nasu Y;Takami Y;Moriuchi A;Sakiyama T;Oketani M;Ido A;Tsubouchi H
• 通讯作者: Tsubouchi H

Microenvironment in the repair process of injured livers accelerates development of hepatocellular carcinoma

受损肝脏修复过程中的微环境加速肝细胞癌的发展

• 发表时间: 2013
• 作者: Tabu;K;Ido A;Kumagai K;Oda Kohei;Mawatari S;Tamai T;Moriuchi A;Uto H;Oketani M;Tsubouchi H
• 通讯作者: Tsubouchi H