The role of osteopontin in d-galactosamine-induced liver injury in genetically obese mice

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Title
The role of osteopontin in d-galactosamine-induced liver injury in genetically obese mice
Author(s)
Hyo Jung Kwon; Young Suk WonWoon Kee YoonKi Hoan Nam; D Y Kim; Hyoung-Chin Kim
Bibliographic Citation
Toxicology and Applied Pharmacology, vol. 242, no. 3, pp. 344-351
Publication Year
2010
Abstract
Various epidemiological studies have shown that obesity increases the risk of liver disease, but the precise mechanisms through which this occurs are poorly understood. In the present study, we hypothesized that osteopontin (OPN), an extracellular matrix and proinflammatory cytokine, has an important role in making obese mice more susceptible to inflammatory liver injury. After exposure of genetically obese ob/ob and db/db mice to a single dose of d-galactosamine (GalN), the plasma liver enzyme levels, histology and expression levels of cytokines and OPN were evaluated. The ob/ob and db/db mice, which were more sensitive to GalN-induced inflammatory liver injury compared with wild-type mice, had significantly higher plasma and hepatic OPN expression levels. Increased OPN expression was mainly found in hepatocytes and inflammatory cells and was correlated with markedly up-regulated interleukin (IL)-12 and IL-18 levels. Furthermore, pretreatment with a neutralizing OPN (nOPN) antibody attenuated the GalN-induced inflammatory liver injury in ob/ob and db/db mice, which was accompanied by significantly reduced macrophages recruitment and IL-12 and IL-18 productions. Taken together, these results suggest that up-regulated OPN expression is a contributing factor to increased susceptibility of genetically obese mice to GalN-induced liver injury by promoting inflammation and modulating immune response.
Keyword
d-GalactosamineInterleukin-12Interleukin-18Obese miceOsteopontin
ISSN
0041-008X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.taap.2009.11.006
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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