Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Preisegger, KH; Factor, VM; Fuchsbichler, A; Stumptner, C; Denk, H; Thorgeirsson, SS.
Atypical ductular proliferation and its inhibition by transforming growth factor beta1 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease.
Lab Invest. 1999; 79(2):103-109
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- Führende Autor*innen der Med Uni Graz
- Preisegger Karl Heinz
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Stumptner Cornelia
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- Abstract:
- Many acute and chronic liver diseases are often associated with atypical ductular proliferation (ADP). These ADPs have gained increasing interest since a number of recent observations suggest that ADPs may represent progenies of the putative liver stem cell compartment. In this study, we show that feeding mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in persistent proliferation of primitive ductules with poorly defined lumens. Similar to oval cell proliferation in other rodent models as well as in various human liver diseases, DDC-induced ADP originated from the portal tract, spread into the hepatic lobule, and was associated closely with appearance of hepatocytes harboring an antigen (A6), which normally is expressed in biliary epithelium. Furthermore, DDC treatment severely inhibited the regenerative capacity of mice after partial hepatectomy. The development of ADP was selectively blocked in DDC-fed TGF-beta1 transgenic mice producing active TGF-beta1 in the liver and no accumulation of new hepatocytes expressing the A6 antigen was observed. Moreover, the transforming growth factor beta1 (TGF-beta1) transgenic mice did not survive beyond 3 weeks from starting the DDC-containing diet. The results suggest that persistent activation of the hepatic stem cell compartment is essential for liver regeneration in the DDC model and that active TGF-beta1 may negatively control activation of stem cells in the liver. These data further emphasize the relevance of the DDC model as an experimental tool for studying chronic liver diseases.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bile Ducts, Intrahepatic - drug effects
- Cell Division - drug effects
- Chronic Disease - drug effects
- Common Bile Duct - drug effects
- Dicarbethoxydihydrocollidine - drug effects
- Disease Models, Animal - drug effects
- Epithelial Cells - pathology
- Hepatectomy - methods
- Ligation - methods
- Liver - drug effects
- Liver Diseases - chemically induced
- Liver Diseases, Alcoholic - pathology
- Liver Regeneration - drug effects
- Mice - drug effects
- Mice, Transgenic - genetics
- Transforming Growth Factor beta - genetics