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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Bettermann, K; Mehta, AK; Hofer, EM; Wohlrab, C; Golob-Schwarzl, N; Svendova, V; Schimek, MG; Stumptner, C; Thuringer, A; Speicher, MR; Lackner, C; Zatloukal, K; Denk, H; Haybaeck, J.
Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A model of steatohepatitis-associated liver carcinogenesis
ONCOTARGET. 2016; 7(45): 73309-73322. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bettermann Kira
Golob-Schwarzl Nicole
Haybäck Johannes
Lackner Karoline
Mehta Anita Kuldeep
Schimek Michael G.
Speicher Michael
Stumptner Cornelia
Svendova Vendula
Zatloukal Kurt
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Number of Figures: 7
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Abstract:
Backround: Steatohepatitis (SH)-associated liver carcinogenesis is an increasingly important issue in clinical medicine. SH is morphologically characterized by steatosis, hepatocyte injury, ballooning, hepatocytic cytoplasmic inclusions termed Mallory-Denk bodies (MDBs), inflammation and fibrosis. 17-20-months-old Krt18-/- and Krt18+/- mice in contrast to wt mice spontaneously developed liver lesions closely resembling the morphological spectrum of human SH as well as liver tumors. The pathologic alterations were more pronounced in Krt18-/- than in Krt18+/- mice. The frequency of liver tumors with male predominance was significantly higher in Krt18-/- compared to age-matched Krt18+/- and wt mice. Krt18-deficient tumors in contrast to wt animals displayed SH features and often pleomorphic morphology. aCGH analysis of tumors revealed chromosomal aberrations in Krt18-/- liver tumors, affecting loci of oncogenes and tumor suppressor genes. Livers of 3-, 6-, 12- and 17-20-months-old aged wild type (wt), Krt18+/- and Krt18-/- (129P2/OlaHsd background) mice were analyzed by light and immunofluorescence microscopy as well as immunohistochemistry. Liver tumors arising in aged mice were analyzed by array comparative genomic hybridization (aCGH). Our findings show that K18 deficiency of hepatocytes leads to steatosis, increasing with age, and finally to SH. K18 deficiency and age promote liver tumor development in mice, frequently on the basis of chromosomal instability, resembling human HCC with stemness features.

Find related publications in this database (Keywords)
Steatohepatitis
Keratin 18 deficiency
Liver tumors
Mallory-Denk bodies
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