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SHR Neuro Krebs Kardio Lipid

Chen, Y; Guldiken, N; Spurny, M; Mohammed, HH; Haybaeck, J; Pollheimer, MJ; Fickert, P; Gassler, N; Jeon, MK; Trautwein, C; Strnad, P.
Loss of keratin 19 favours the development of cholestatic liver disease through decreased ductular reaction.
J Pathol. 2015; 237(3):343-354
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Autor/innen der Med Uni Graz:
Fickert Peter
Haybäck Johannes
Pollheimer Marion
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Abstract:
Keratins (K) are cytoprotective proteins and keratin mutations predispose to the development of multiple human diseases. K19 represents the most widely used marker of biliary and hepatic progenitor cells as well as a marker of ductular reaction that constitutes the basic regenerative response to chronic liver injury. In the present study, we investigated the role of K19 in biliary and hepatic progenitor cells and its importance for ductular reaction. K19 wild-type (WT) and knockout (KO) mice were fed: (a) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC); (b) cholic acid (CA); (c) a choline-deficient, ethionine-supplemented (CDE) diet; or (d) were subjected to common bile duct ligation (CBDL). The bile composition, liver damage, bile duct proliferation, oval cell content and biliary fibrosis were analysed. In untreated animals, loss of K19 led to redistribution of the K network in biliary epithelial cells (BECs) but to no obvious biliary phenotype. After DDC feeding, K19 KO mice exhibited (compared to WTs): (a) increased cholestasis; (b) less pronounced ductular reaction with reduced ductular proliferation and fewer oval cells; (c) impaired Notch 2 signalling in BECs; (d) lower biliary fibrosis score and biliary bicarbonate concentration. An attenuated oval cell proliferation in K19 KOs was also found after feeding with the CDE diet. K19 KOs subjected to CBDL displayed lower BEC proliferation, oval cell content and less prominent Notch 2 signal. K19 deficiency did not change the extent of CA- or CBDL-induced liver injury and fibrosis. Our results demonstrate that K19 plays an important role in the ductular reaction and might be of importance in multiple chronic liver disorders that frequently display a ductular reaction. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Proliferation -
Chemical and Drug Induced Liver Injury - etiology
Chemical and Drug Induced Liver Injury - genetics
Chemical and Drug Induced Liver Injury - metabolism
Chemical and Drug Induced Liver Injury - pathology
Cholangitis, Sclerosing - chemically induced
Cholangitis, Sclerosing - genetics
Cholangitis, Sclerosing - metabolism
Cholangitis, Sclerosing - pathology
Cholestasis, Extrahepatic - etiology
Cholestasis, Extrahepatic - genetics
Cholestasis, Extrahepatic - metabolism
Cholestasis, Extrahepatic - pathology
Cholic Acid -
Choline Deficiency - complications
Common Bile Duct - metabolism
Common Bile Duct - pathology
Common Bile Duct - surgery
Disease Models, Animal -
Epithelial Cells - metabolism
Epithelial Cells - pathology
Ethionine -
Keratin-19 - deficiency
Keratin-19 - genetics
Ligation -
Liver - metabolism
Liver - pathology
Liver Cirrhosis, Biliary - chemically induced
Liver Cirrhosis, Biliary - genetics
Liver Cirrhosis, Biliary - metabolism
Liver Cirrhosis, Biliary - pathology
Liver Regeneration -
Male -
Mice, Knockout -
Phenotype -
Pyridines -
Signal Transduction -
Stem Cells - metabolism
Stem Cells - pathology
Time Factors -

Find related publications in this database (Keywords)
cholangitis
ductular reaction
intermediate filament
stem cell
DDC
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