Next Article in Journal
Proteomic Analysis of Mitochondria-Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda-1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2)
Previous Article in Journal
Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector
Previous Article in Special Issue
Regulation of Ketone Body Metabolism and the Role of PPARα
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 18
Issue 2
10.3390/ijms18020434
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

by
Anna Kakehashi
1,*,
Vasily E. Stefanov
2,
Naomi Ishii
1,
Takahiro Okuno
1,
Hideki Fujii
3,
Kazuaki Kawai
4,
Norifumi Kawada
3 and
Hideki Wanibuchi
1
1
Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan
2
Department of Biochemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia
3
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
4
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(2), 434; https://doi.org/10.3390/ijms18020434
Submission received: 12 December 2016 / Revised: 24 January 2017 / Accepted: 9 February 2017 / Published: 17 February 2017
(This article belongs to the Special Issue Linking Nutrition and Energy Metabolism: Roles of PPARs in Healthy and in Disrupted Metabolic Homeostasis)
Browse Figures
Versions Notes

Abstract

To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.
Keywords: nonalcoholic steatohepatitis (NASH); hepatocellular carcinoma; biopsy; PPARs; β-catenin; cytokeratins 8/18; NRIP1; oxidative stress nonalcoholic steatohepatitis (NASH); hepatocellular carcinoma; biopsy; PPARs; β-catenin; cytokeratins 8/18; NRIP1; oxidative stress
Graphical Abstract

Share and Cite

MDPI and ACS Style

Kakehashi, A.; Stefanov, V.E.; Ishii, N.; Okuno, T.; Fujii, H.; Kawai, K.; Kawada, N.; Wanibuchi, H. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas. Int. J. Mol. Sci. 2017, 18, 434. https://doi.org/10.3390/ijms18020434

AMA Style

Kakehashi A, Stefanov VE, Ishii N, Okuno T, Fujii H, Kawai K, Kawada N, Wanibuchi H. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas. International Journal of Molecular Sciences. 2017; 18(2):434. https://doi.org/10.3390/ijms18020434

Chicago/Turabian Style

Kakehashi, Anna, Vasily E. Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, and Hideki Wanibuchi. 2017. "Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas" International Journal of Molecular Sciences 18, no. 2: 434. https://doi.org/10.3390/ijms18020434

APA Style

Kakehashi, A., Stefanov, V. E., Ishii, N., Okuno, T., Fujii, H., Kawai, K., Kawada, N., & Wanibuchi, H. (2017). Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas. International Journal of Molecular Sciences, 18(2), 434. https://doi.org/10.3390/ijms18020434

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop