Increased expression of c-Jun in nonalcoholic fatty liver disease
Dorn C, Engelmann JC, Saugspier M, Koch A, Hartmann A, Mueller M, Spang R, Bosserhoff A, Hellerbrand C (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
Book Volume: 94
Pages Range: 394-408
Journal Issue: 4
Abstract
Overnutrition is the major cause of nonalcoholic fatty liver disease (NAFLD) and its advanced form nonalcoholic steatohepatitis (NASH). We aimed to develop and characterize a murine model, which resembles both the pathology and nutritional situation, of NASH patients in Western societies. Mice were fed with a NASH-inducing diet (ND) containing sucrose, cholesterol and fats rich in saturated fatty acids in a composition, which mimics Western food. After 12 weeks, ND-fed mice revealed obesity and impaired glucose tolerance. In the liver, ND-feeding led to marked steatosis, hepatocellular damage, inflammation and beginning fibrosis. Transcriptome-wide gene expression analysis and search for over-represented transcription factor target sites among the differentially expressed genes identified activator protein-1 (AP-1) as the most likely factor to cause the transcriptional changes in ND livers. Combining differentially expressed gene and protein-protein interaction network analysis identified c-Jun as hub in the largest connected deregulated sub-network in ND livers. Accordingly, ND livers revealed c-Jun-phosphorylation and nuclear translocation. Moreover, hepatic c-Jun expression was enhanced in ND-fed mice. Combined tissue microarray technology and immunohistochemical analysis confirmed enhanced hepatic c-Jun levels in NAFLD patients, which correlated with inflammation, and notably, with the degree of hepatic steatosis. In summary, our new mouse model shows important pathological changes also found in human NASH and indicates c-Jun/AP-1 activation as critical regulator of hepatic alterations. Abundance of c-Jun in NAFLD likely facilitates development and progression of NASH.
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Germany (DE)How to cite
APA:
Dorn, C., Engelmann, J.C., Saugspier, M., Koch, A., Hartmann, A., Mueller, M.,... Hellerbrand, C. (2014). Increased expression of c-Jun in nonalcoholic fatty liver disease. Laboratory Investigation, 94(4), 394-408. https://doi.org/10.1038/labinvest.2014.3
MLA:
Dorn, Christoph, et al. "Increased expression of c-Jun in nonalcoholic fatty liver disease." Laboratory Investigation 94.4 (2014): 394-408.
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