Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitis |
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Authors: | Henkel Corinna Roderfeld Martin Weiskirchen Ralf Berres Marie-Luise Hillebrandt Sonja Lammert Frank Meyer Helmut E Stühler Kai Graf Jürgen Roeb Elke |
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Institution: | University Hospital Giessen & Marburg, Campus Giessen, Department of Medicine II, Gastroenterology, Giessen, Germany. elke.roeb@innere.med.uni-giessen.de |
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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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Keywords: | Detoxification DIGE Hepatic fibrosis Liver Selenium‐binding protein |
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