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Title 

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

Authors 

Hyo Jung KwonYoung Suk WonWoon Kee YoonKi Hoan NamD Y KimHyoung-Chin Kim

Publisher 

Elsevier

Issue Date 

2010

Citation 

Toxicology and Applied Pharmacology, vol. 242, no. 3, pp. 344-351

Keywords 

d-GalactosamineInterleukin-12Interleukin-18Obese miceOsteopontin

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.

ISSN 

0041-008X

Link 

http://dx.doi.org/10.1016/j.taap.2009.11.006

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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