Proteome analysis of heterogeneity of intrahepatic biliary epithelial cells

• Project/Area Number: 16590573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: UENO Yoshiyuki TOHOKU UNIVERSITY, HOSPITAL, Lecturer, 病院, 講師 (70282126)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
• Keywords: cholangiocyte / primary biliary cirrhosis / proteomic analysis / animal model / aquaporine / 肝内胆管細胞 / Ebhrin / 不死化細胞

Research Abstract

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.

Research Products

• [Journal Article] The limited role of bone marrow cells in experimental cholestatic ductal hyperplasia. (2006)
  • Author(s): Moritoki Y, Ueno Y, Kanno A, Yamagiwa Y, Fukushima K, Shimosegawa T.
  • Journal Title: Liver International 26 Pages: 457-66
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Beta 1 and beta 2 adrenergic receptor agonists prevent bile duct injury induced by adrenergic denervation by increased cAMP levels and activation of Akt. (2006)
  • Author(s): Glaser S, Alvaro D, Francis H, Ueno Y, Marucci L, Benedetti A, De Marrow S, Marzioni M, Mancino MG, Phinizy JL, Reichenbach R, Fava G, Summers R, Venter J, Alpini G
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 290
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ca-dependent cytoprotective effects of urso-and tauroursodeoxycholic acid on the biliary epithelium in a rat model of cholestasis and loss of bile ducts. (2006)
  • Author(s): Marzioni M, Francis H, Benedetti A, Ueno Y, Fava G, Venter J, Reichenbach R, Mancino MG, Summers R, Alpini G, Glaser S
  • Journal Title: Am J Pathology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The bioinformatic approach for understanding the heterogeneity of cholangiocytes. (2006)
  • Author(s): Fukushima K, Ueno Y
  • Journal Title: World J Gastroenterology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Differential expressions of aquaporin proteins in human cholestatic liver diseases. (2006)
  • Author(s): Tamai K, Fukushima K, Ueno Y, Moritoki Y, Yamagiwa Y, Kanno N, Jefferson DM, Shimosegawa T.
  • Journal Title: Hepatol Res 34 Pages: 99-103
  • NAID: 10020405804
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Over-expression of Interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes. (2006)
  • Author(s): Meng F, Yamagiwa Y, Ueno Y, Patel T
  • Journal Title: J Hepatol (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. (2006)
  • Author(s): Gaudio E, Barbaro B, Alvaro D, Glaser S, Francis H, Ueno Y, Meininger CJ, Franchitto A, Onori P, Marzioni M, Taffetani S, Fava G, Stoica G, Venter J, Reichenbach R, De Mrrow S, Summers R, Alpini G
  • Journal Title: Gastroenterology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Beta 1 and Beta 2 adrenergic receptor agonists prevent bile duct injury induced by adrenergic denervation by increased cAMP levels and activation of Akt. (2006)
  • Author(s): Glaser S, Alvaro D, Francis F, Ueno Y, Marucci L, Benedetti A, Marzioni M, De Morrow, S, Mancino MG, Phinizy JL, Reichenbach R, Fava G, Summers R, Venter J, Alpini G.
  • Journal Title: Am J Pathology 290
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The limited role of bone marrow cells in experimental cholestatic ductal hyperplasia. (2006)
  • Author(s): Moritoki Y, Ueno Y, Kanno A, Yamagiwa Y, Fukushima K, Shimosegawa T.
  • Journal Title: Liver International (in press)
• [Journal Article] Beta 1 and beta 2 adrenergic receptor agonists prevent bile duct injury induced by adrenergic denervation by increased cAMP levels and activation of Akt. (2006)
  • Author(s): Glaser S, Alvaro D, Francis H, Ueno Y, Marucci L, Benedetti A, De Manow S, Marzioni M, Mancino MG, Phinizy JL, Reichenbach R, Fava G, Summers R, Venter J, Alpini G
  • Journal Title: Am J Physiol Gastrointest Liver Physiol (in press)
• [Journal Article] Differential expressions of aquaporin proteins in human cholestatic liver diseases. (2006)
  • Author(s): Tamai K, Fukushima K, Ueno Y, Moritoki Y, Yamagiwa Y, Kanno N, Jefferson DM, Shimosegawa T.
  • Journal Title: Hepatol Res (in press)
  • NAID: 10020405804
• [Journal Article] Tannic Acid Inhibits Cholangiocyte Proliferation after Bile Duct Ligation via a Cyclic Adenosine 5',3'-Monophosphate-Dependent Pathway. (2005)
  • Author(s): Taffetani S, Ueno Y, Meng F, Venter J, Francis H, Glaser S, Alpini G, Patel T.
  • Journal Title: Am J Pathology 166 Pages: 1671-80
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Autocrine/paracrine regulation of the growth of the bilisry tree by the neuroendocrine hormone serotonin. (2005)
  • Author(s): Marzioni M, Glaser S, Francis H, Marrucci L, Benedetti A, Alvaro D, Taffetani S, Ueno Y, Roskams T, Phinizy JL, Venter J, Fava G, Lesage GD, Alpini G
  • Journal Title: Gastroenterology 128 Pages: 121-37
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Autocrine/paracrine regulation of the growth of the biliary tree by the neuroendocrine hormone serotonin. (2005)
  • Author(s): Marzioni M, Glaser S, Francis H, Marucci L, Benedetti A, Alvaro D, Taffetani S, Ueno Y, Roskams T, Phinizy JL, Venter J, Fava G, Lesage GD, Alpini G.
  • Journal Title: Gastroenterology 128 Pages: 121-137
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tannic Acid Inhibits Cholangiocyte Proliferation after Bile Duct Ligation via a Cyclic Adenosine 5', 3'-Monophosphate-Dependent Pathway. (2005)
  • Author(s): Taffetani S, Ueno Y, Meng F, Venter J, Fancis H.Glaser S, Alnini G, Patel T.
  • Journal Title: Am J Pathology 166 Pages: 1671-1680
• [Journal Article] Translational regulation of XIAP expression and cell survival during hypoxia in human cholangiocarcinoma. (2004)
  • Author(s): Marienfeld C, Yamagiwa Y, Ueno Y, Brooks L, Meng F, Patel T
  • Journal Title: Gastroenterology 127 Pages: 1198-209
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)-and PKC-dependent stimulation og cAMP. (2004)
  • Author(s): 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
  • Journal Title: Gastroenterology 127 Pages: 1787-97
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nerve growth factor modulates the proliferative capacity of the intrahepatic biliary epithelium inexperimental cholestasis. (2004)
  • Author(s): 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
  • Journal Title: Hepatology 40 Pages: 1116-27
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] cAMP stimulates the secretory and proliferativecapacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 psthway. (2004)
  • Author(s): Francis H, Glaser S, Ueno Y, Lesage G, Marucci L, Benedetti A, Taffetani S, Marzioni M, Alvaro D, Venter J, Reichenbach R, Fava G, Lynne Phinizy J, Alpini G
  • Journal Title: J Hepatol 41 Pages: 528-37
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Translational regulation of XIAP expression and cell survival during hypoxia in humann cholangiocarcinoma. (2004)
  • Author(s): Marienfeld C, Yamagiwa Y, Ueno Y, Chiasson V, Brooks L, Meng F, Patel T.
  • Journal Title: Gastroenterology 127 Pages: 1787-1797
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)- and PKC-dependent stimulation of cAMP. (2004)
  • Author(s): LeSage GD, Alvaro D, Glaser S, Francis H, Marucci L, Roskams T, Phinizy JL, Marzioni M, Benedetti A, Taffetani S, Barbaro B, Fava G, Ueno Y, Alpini G.
  • Journal Title: Gastroenterology 127 Pages: 1198-1209
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nerve growth factor modulates the proliferative capacity of the intrahepatic biliary epithelium in experimnental cholestasis. (2004)
  • Author(s): 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.
  • Journal Title: Hepatology 40 Pages: 1116-1127
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway. (2004)
  • Author(s): Francis H, Glaser S, Ueno Y, Lesage G, Marucci L, Benedetti A, Taffetani S, Marzioni M, Alvaro D, Venter J, Reichenbach R, Fava G, Lynne Phinizy J, Alpini G.
  • Journal Title: J Hepatol 41 Pages: 528-537
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Translational regulation of XIAP expression and cell survival during hypoxia in human cholangiocarcinoma. (2004)
  • Author(s): Marienfeld C, Yamagiwa Y, Ueno Y, Chiasson V, Brooks L, Meng F, Patel T.
  • Journal Title: Gastroenterology 127 Pages: 1787-1797
• [Journal Article] alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)- and PKC-dependent stimulation of cAMP. (2004)
  • Author(s): LeSage GD, Alvaro D, Glaser S, Taffetani S, Barbaro B, Fava G, Ueno Y, Alpini G.
  • Journal Title: Hepatology 40 Pages: 1116-1127
• [Journal Article] Nerve growth factor modulates the proliferative capacity of the intrahepatic biliary epithelium in experimental cholestasis. (2004)
  • Author(s): Gigliozzi A, Alpini G, Baroni GS, Francis H, Mancino MG, Ueno Y, Barbaro B, Benedetti A, Attili AF, Alvaro D.
  • Journal Title: Gastroenterology 127 Pages: 1198-1209
• [Journal Article] cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway. (2004)
  • Author(s): Francis H, Glaser S, Ueno Y, Lesage G, Fava G, Lynne Phinizy J, Alpini G.
  • Journal Title: J Hepatol 41 Pages: 528-537
• [Journal Article] Ca-dependent cytoprotective effects of urso-and tauroursodeoxycholic acid on the biliary epithelium in a rat model of cholestasis and loss of bile ducts.
  • Author(s): Marzioni M, Francis H, Benedetti A, Ueno Y, Fava G, Venter J, Reichenbach R, Mancino MG, Summers R, Alpini G, Glaser S
  • Journal Title: Am J Pathology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The bioinformatic approach for understanding the heterogeneity of cholangiocytes.
  • Author(s): Fukushima K, Ueno Y
  • Journal Title: World J Gastroenterology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Over-expression of Interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes.
  • Author(s): Meng F, Yamagiwa Y, Ueno Y, Patel T.
  • Journal Title: J Hepatol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vasculat endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism
  • Author(s): Gaudio E, Barbaro B, Alvaro D, Glaser S, Francis H, Ueno Y, Meininger CJ, Franchitto A, Onori P, Marzioni M, Taffetani S, Fava G, Stoica G, Venter J, Reichenbach R, De Morrow S, Summers R, Alpini G
  • Journal Title: Gastroenterology (in press)
  • Description: 「研究成果報告書概要(欧文)」より