Proteome analysis of heterogeneity of intrahepatic biliary epithelial cells

肝内胆管上皮细胞异质性的蛋白质组分析

• 批准号: 16590573
• 负责人: UENO Yoshiyuki
• 金额: $ 2.37万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590573/
• 关键词: cholangiocyte; primary biliary cirrhosis; proteomic analysis; animal model; aquaporine; 肝内胆管細胞; Ebhrin; 不死化細胞

It is remarkable that microarray technologies have nearly reached a pinnacle. Establishment of further analysis and management of enormous data derived from microarray technology is currently the highest priority. The heterogeneous functions of cholangiocytes regulate the pathophysiology of the biliary epithelium regarding secretory, proliferative and apoptotic activities. Distinct expression profiles of two murine cholangiocytes lines, termed small and large were revealed by microarray analysis. The features of the two cholangiocyte cell lines, categorized partly according to gene ontology, indicate the specific physiological role of each cell lines. Namely large cholangiocytes are characterized as "transport" and "immune/inflammatory responses". In contrast to large, small cholangiocytes are associated with properties of limited physiological functional ability and proliferating/migrating potential with specific molecules like Eph receptors, comparable to mesenchymal cells. 'Omic study will be of great help to understanding the heterogeneiety of cholangiocytes. In the current study, we have performed the basic conditioning study for proteomic study of cholangiocyte by 1)establishing isolation technique from surgically obtained liver tissue, 2)developing novel culture methods by transfection of SV40 large T antigen, 3)developing stem cell transplantation model using EGFP-transgenic mice. With these novel methods, further evaluation of cholangiocytes specific expression profile could be determined.

值得注意的是，微阵列技术几乎达到了顶峰。建立对来自微阵列技术的大量数据的进一步分析和管理是目前的最高优先事项。胆管细胞的异质性功能调节胆管上皮的分泌、增殖和凋亡活动的病理生理学。微阵列分析揭示了两个小鼠胆管细胞系，称为小和大的不同的表达谱。两种胆管细胞系的特征，部分根据基因本体分类，表明每个细胞系的特定生理作用。即，大胆管细胞的特征在于“运输”和“免疫/炎症反应”。与大的相反，小的胆管细胞与有限的生理功能能力和特定分子如Eph受体的增殖/迁移潜力的性质相关，与间充质细胞相当。OMIC研究对了解胆管细胞的异质性有很大帮助。本研究通过建立肝组织分离技术、SV 40大T抗原转染培养方法、EGFP转基因小鼠肝细胞干细胞移植模型，为胆管细胞蛋白质组学研究奠定了基础。利用这些新的方法，可以确定胆管细胞特异性表达谱的进一步评估。

项目成果

Translational regulation of XIAP expression and cell survival during hypoxia in human cholangiocarcinoma

• DOI: 10.1053/j.gastro.2004.09.002
• 发表时间: 2004-12-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Marienfeld, C;Yamagiwa, Y;Patel, T
• 通讯作者: Patel, T

Nerve growth factor modulates the proliferative capacity of the intrahepatic biliary epithelium inexperimental cholestasis.

神经生长因子在实验性胆汁淤积中调节肝内胆管上皮的增殖能力。

• 发表时间: 2004
• 期刊: Hepatology 40
• 作者: Gigliozzi A;Alpini G;Baroni GS;Marucci L;Metalli VD;Glaser SS;Francis H;Mancino MG;Ueno Y;Barbaro B;Benedetti A;Attili AF;Alvaro D
• 通讯作者: Alvaro D

Differential expressions of aquaporin proteins in human cholestatic liver diseases.

• DOI: 10.1016/j.hepres.2005.11.006
• 发表时间: 2006-02
• 期刊: Hepatology research : the official journal of the Japan Society of Hepatology
• 作者: Keiichi Tamai;K. Fukushima;Y. Ueno;Y. Moritoki;Y. Yamagiwa;N. Kanno;D. Jefferson;T. Shimosegawa

cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway

• DOI: 10.1016/j.jhep.2004.06.009
• 发表时间: 2004-10-01
• 期刊: JOURNAL OF HEPATOLOGY
• 影响因子: 25.7
• 作者: Francis, H;Glaser, S;Alpini, G
• 通讯作者: Alpini, G

Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)-and PKC-dependent stimulation og cAMP.

Alpha-1 肾上腺素能受体激动剂通过 Ca(2) 和 PKC 依赖性刺激 og cAMP 调节 BDL 大鼠的导管分泌。

• 发表时间: 2004
• 期刊: Gastroenterology 127
• 作者: LeSage GD;Alvaro D;Glaser S;Francis H;Marucci L;Roskams T;Phinizy JL;Marzioni M;Benedetti A;Taffetani S;Marbaro B;FavaG;Ueno Y;Alpini G
• 通讯作者: Alpini G