The role of intermediateted filament proteins in hepatic stellate cells in the development of liver fibrosis and hepatocellular carcinoma

肝星状细胞中间丝蛋白在肝纤维化和肝细胞癌发生中的作用

• 批准号: 18591513
• 负责人: UYAMA Naoki
• 金额: $ 2.48万
• 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: 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-18591513/
• 关键词: Intermediate filament; liver fibrois; hepatic stellate cells; hepatocellular carcinoma; synemin; vimentin

(A) Expression of Intermediate filament proteins by rat hepatic stellate cells.Expression of intermediated filament proteins in rat normal or cirrhotic liver tissues was investigated. In normal liver, GFAP, desmin, vimentin and synemin were expressed by hepatic stellate cells. In cirrhotic liver, expression of GFAP and synemin was down-regulated and expression of desmin and vimentin was up-regulated. Isolated stellate cells from rat liver are thought to be activated during the culture on the plastic dish. Expression of GFAP and synemin was down-regulated and expression of desmin and vimentin was up-regulated during the culture. So, we found that quiescent rat stellate cells express synmin and GFAP and activated stellate cells express desmin and vimentin.(B) Expression of Intermediate filament proteins by human hepatic stellate cells.Expression of GFAP, synemin, desmin and vimentin in human normal or cirrhotic liver tissues was investigated. In normal liver, vimentin and synemin were expressed by hepatic stellate cells. However, desmin and GFAP were not expressed by hepatic stellate cells. In cirrhotic liver, expression of synemin was down-regulated and expression of vimentin was up-regulated. In LX-2 cells, cell line of stellate cells, Expression of vimentin, but not synemin, detected. So, we found that synmin and vimentin play a key role to regulate the activation of hepatic stellate cells.(C) The role of vimentin in human hepatic stellate cells.We investigated the role of vimentin in human hepatic stellate cells. Expression of vimentin in LX-2 cells were down regulated by 85% of control by siRNAs. Depletion of vimentin did not affect the ability to proliferate and the expression of type I collagen. In the future, we will investigate the function of vimentin in human hepatic stellate cells again by other methods.

(A)大鼠肝星状细胞中间丝蛋白的表达研究了中间丝蛋白在大鼠正常和肝硬化组织中的表达。在正常肝脏中，肝星状细胞表达GFAP、结蛋白、波形蛋白和突触蛋白。肝纤维化时GFAP和synemin表达下调，desmin和vimentin表达上调。从大鼠肝脏分离的星状细胞被认为在塑料培养皿上培养期间被激活。GFAP和synemin的表达在培养过程中下调，结蛋白和波形蛋白的表达上调。因此，我们发现静止的大鼠星状细胞表达synmin和GFAP，而活化的星状细胞表达结蛋白和波形蛋白。(B)人肝星状细胞中间丝蛋白的表达研究了GFAP、synemin、desmin和vimentin在人正常肝组织和肝硬化组织中的表达。在正常肝脏，波形蛋白和synemin表达的肝星状细胞。肝星状细胞不表达结蛋白和GFAP。在急性肝损伤中，synemin表达下调，vimentin表达上调。在星形细胞系LX-2细胞中，检测到波形蛋白的表达，但未检测到突触蛋白。因此，我们发现synmin和vimentin在调节肝星状细胞的活化中起关键作用。(C)波形蛋白在人肝星状细胞中的作用我们研究了波形蛋白在人肝星状细胞中的作用。结果显示，波形蛋白在LX-2细胞中的表达下调了85%。波形蛋白的消耗并不影响增殖能力和I型胶原的表达。今后，我们将通过其他方法再次研究波形蛋白在人肝星状细胞中的功能。

项目成果

Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein

• DOI: 10.1016/j.jamcollsurg.2005.11.012
• 发表时间: 2006-03-01
• 期刊: JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
• 影响因子: 5.2
• 作者: Ikai, I;Hatano, E;Shimahara, Y
• 通讯作者: Shimahara, Y

Expression and function of synemin in rat and human hepatic stellate cells

Synemin在大鼠和人肝星状细胞中的表达和功能

• 发表时间: 2007
• 作者: Uyama;N
• 通讯作者: N

切除不能肝細胞癌に対するアイエーコールを用いた肝動脈化学塞栓療法の治療効果及び有害事象の検討

IECOL肝动脉化疗栓塞治疗不可切除性肝细胞癌的疗效及不良反应观察

• 发表时间: 2007
• 作者: Uyama;N;宇山 直樹;宇山 直樹
• 通讯作者: 宇山 直樹

Expression of somatostatin receptors in splanchnic blood vessels of normal and cirrhotic rats

• DOI: 10.1111/j.1478-3231.2007.01503.x
• 发表时间: 2007-08
• 期刊: Liver International
• 影响因子: 6.7
• 作者: H. Reynaert;E. Van Rossen;N. Uyama;N. Chatterjee;U. Kumar;D. Urbain;A. Geerts

Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats

• DOI: 10.1136/gut.2006.092460
• 发表时间: 2007-05-01
• 期刊: GUT
• 影响因子: 24.5
• 作者: Kinoshita, Kohji;Iimuro, Yuji;Ikeda, Kazuo
• 通讯作者: Ikeda, Kazuo