期刊
PROSTAGLANDINS & OTHER LIPID MEDIATORS
卷 92, 期 1-4, 页码 54-61出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2010.03.001
关键词
5-Lipoxygenase; Knockout mice; Lipid metabolism
资金
- Ministerio de Ciencia e Innovacion (MICINN) [SAF 06/03191, SAF 09/08767]
- Instituto de Salud Carlos III
- Generalitat de Catalunya-European Social Funds [2006FI-00091]
Five-lipoxygenase (5-LO) has been postulated as a pathogenic factor in liver injury. Indeed, Alox5, the gene coding for 5-LO, is heavily over-expressed in experimental liver disease, in which 5-LO inhibition consistently ameliorates hepatic steatosis, inflammation and fibrosis. Herein, we report the findings in mice with targeted deletion of Atox5 as a proof of concept of the role of 5-LO in liver injury. Our findings demonstrate that ablation of Alox5 in mice confers protection against carbon tetrachloride-induced liver injury since hepatic necroinflammation, inflammatory infiltrate, hepatocyte ballooning and serum ALT levels were significantly reduced in Alox5-deficient mice. These mice also showed a lower degree of hepatic steatosis, which affected micro- and macrosteatosis to a similar extent. Moreover, microarray analysis revealed a differential profile of hepatic gene expression in Alox5-deficient mice, with a total of 117 genes differentially expressed in these animals. Functional grouping of these genes revealed that 28 (approximately 24% of total changes) were related to the category of lipid metabolism, including the lipogenic factors Lpin1, C/EBP, Fasn, Acly and Elov16. Moreover, Ingenuity Pathway Analysis revealed lipid metabolism as the molecular/cellular function most affected by the loss of Alox5. These findings confirm at a genetic level that Alox5 plays a pathogenic role in the response of the liver to injury. (C) 2010 Elsevier Inc. All rights reserved.
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