Z Gastroenterol 2019; 57(01): e50-e51
DOI: 10.1055/s-0038-1677180
3. Metabolism (incl. NAFLD)
Georg Thieme Verlag KG Stuttgart · New York

Loss of zonation in end stage liver disease revealed by in situ omics

F Reichel
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
,
M Brosch
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
,
K Kattler
2   Department of Genetics & Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
A Herrmann
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
,
W von Schönfels
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
K Nordström
2   Department of Genetics & Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
D Seehofer
4   Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, Leipzig, Germany
,
G Damm
4   Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, Leipzig, Germany
,
T Becker
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
S Zeissig
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
S Nehring
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
V Moser
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
RV Thangapandi
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
,
F Stickel
5   Department of Gastroenterology, University of Zürich, Zürich, Switzerland
,
G Baretton
6   Institute of Pathology, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
C Röcken
7   Institute of Pathology, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
M Muders
6   Institute of Pathology, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
M Matz-Soja
8   Rudolf-Schönheimer-Institute for Biochemistry, University of Leipzig, Leipzig/Germany
,
M Krawczak
10   Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany
,
G Gasparoni
2   Department of Genetics & Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
H Hartmann
11   Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden (TU Dresden), Dresden Germany
,
A Dahl
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
,
C Schafmayer
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
J Walter
2   Department of Genetics & Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
J Hampe
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
9   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

 
 

    Zonation of liver metabolism and its regulation has been intensely studied in the past but was focused on the healthy organ and animal models. Major break throughs were accomplished especially using so called omics-techniques. Although liver cirrhosis has become one of the major problems in the western world, it was not yet achieved to use those methods at this stage of disease progression.

    Here we present the first study on transcriptomes of hepatocytes spatially extracted from human cirrhotic liver samples, innovatively combining the two powerful methods of laser capture microdissection and deep whole genome RNA-sequencing.

    We were able to detect that the functional zonation of the liver lobule and its gradients of enzyme and other protein coding mRNA between the periportal fields and the central vein is completely compromised in the stage of liver cirrhosis. This refers to plenty of key enzymes of the major pathways of the metabolism of the liver including the expression of glutamine synthetase. This can primarily be explained by the loss of formerly zonation-inducing pathways. The sacrificed zonated Wnt-signaling activity may be a major cause for the loss of a characteristically pericentral gene expression thus leading to the process of portalisation of hepatocytes throughout the liver.

    Overall our data provides a deeper understanding for the deregulation of liver zonation and its consequences for liver functions in end stage liver disease eventually leading to the failure of the organ.


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