Animal Proteomics

Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitis

  1. Corinna Henkel1,†,
  2. Martin Roderfeld1,†,
  3. Ralf Weiskirchen2,
  4. Marie-Luise Berres3,
  5. Sonja Hillebrandt4,
  6. Frank Lammert4,
  7. Helmut E. Meyer5,
  8. Kai Stühler5,
  9. Jürgen Graf6,
  10. Elke Roeb Professor1,*

Article first published online: 15 NOV 2006

DOI: 10.1002/pmic.200600580

Issue

PROTEOMICS

PROTEOMICS

Volume 6, Issue 24, pages 6538–6548, No. 24 December 2006

Additional Information

How to Cite

Henkel, C., Roderfeld, M., Weiskirchen, R., Berres, M.-L., Hillebrandt, S., Lammert, F., Meyer, H. E., Stühler, K., Graf, J. and Roeb, E. (2006), Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitis. Proteomics, 6: 6538–6548. doi: 10.1002/pmic.200600580

Author Information

  1. 1

    University Hospital Giessen & Marburg, Campus Giessen, Department of Medicine II, Gastroenterology, Giessen, Germany

  2. 2

    Institute of Clinical Chemistry and Pathobiochemistry, University Hospital RWTH Aachen, Aachen, Germany

  3. 3

    Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany

  4. 4

    Department of Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany

  5. 5

    Medical Proteom-Center, Ruhr-University of Bochum, Bochum, Germany

  6. 6

    University Hospital Giessen & Marburg, Campus Marburg, Department of Anesthesiology and Intensive Care, Marburg, Germany

  1. †

    These authors contributed equally to this work.

*Medical Clinic II, Gastroenterology, University Hospital JLU Giessen, Paul-Meimberg-Strasse 5, D-35385 Giessen, Germany Fax: +49-641-99-42339

  1. †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 12 DEC 2006
  2. Article first published online: 15 NOV 2006
  3. Manuscript Received: 6 MAR 2006

Funded by

  • Deutsche Forschungsgemeinschaft (SFB 542 TP C3, RO 957/6-1 and LA997/4-1)
  • Federal Ministry of Education and Research of Germany (Network of Competence in Medicine, Hepatitis-Netzwerk), Aachen University (START project Identification of Molecular Markers and Gene Therapy of Fibrosis Wound Healing)
  • Nordrhein Westfalen Ministerium f�r Wissenschaft und Forschung

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Keywords:

  • Detoxification;
  • DIGE;
  • Hepatic fibrosis;
  • Liver;
  • Selenium-binding protein

Abstract

We investigated the changes in the hepatic proteome in murine models for toxic-induced fibrogenesis and sclerosing cholangitis. A comprehensive comparison of protein changes observed is made and the mechanistical basis of the expression changes is discussed. Hepatic fibrosis was induced by repetitive intraperitoneal CCl4 treatment of BALB/c mice or developed spontaneously in BALB/c-ATP-binding cassette, subfamily B, member 4 (Abcb4) knock out mice. Fibrosis was verified by a morphometric score and assessment of hydroxyproline content of liver tissue, respectively. The innovative difference in-gel electrophoresis (DIGE) technique was used to analyse protein expression levels of the mouse proteome. Results were confirmed by Western blotting and real-time RT-PCR. In CCl4-induced fibrosis 20 out of 40 and in BALB/c-Abcb4−/− mice 8 out of 28 differentially expressed proteins were identified utilizing DIGE. Only two proteins, selenium-binding protein (Sbp2) and carbonic anhydrase 3, have been unidirectionally expressed (i.e. down-regulated) in both models. Relevant differences in the pathogenesis of toxically induced liver fibrosis and sclerosing cholangitis exist. The only novel protein with regard to liver fibrosis depicting a unidirectional expression pattern in both animal models was Sbp2. An explicit protein function could not be clarified yet.

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