The role of osteopontin in D-galactosamine-induced liver injury in genetically obese mice
The role of osteopontin in D-galactosamine-induced liver injury in genetically obese mice
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DOI：
10.1016/j.taap.2009.11.006
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发表时间：
2010-02-01
影响因子：
3.8
通讯作者：
Kim, Hyoung-Chin
中科院分区：
文献类型：
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作者：
Kwon, Hyo-Jung;Won, Young-Suk;Kim, Hyoung-Chin
各种流行病学研究表明，肥胖会增加患肝病的风险，但人们对这种情况发生的确切机制知之甚少。在本研究中，我们假设骨桥蛋白（OPN）是一种细胞外基质和促炎细胞因子，在使肥胖小鼠更容易受到炎症性肝损伤方面发挥着重要作用。将遗传性肥胖ob/ob和db/db小鼠暴露于单剂量的D-半乳糖胺(GalN)后，评估血浆肝酶水平、组织学以及细胞因子和OPN的表达水平。与野生型小鼠相比，ob/ob 和 db/db 小鼠对 GaIN 诱导的炎症性肝损伤更敏感，其血浆和肝脏 OPN 表达水平显着较高。 OPN 表达增加主要见于肝细胞和炎症细胞，并与白细胞介素 (IL)-12 和 IL-18 水平显着上调相关。此外，用中和 OPN (nOPN) 抗体预处理可减轻 ob/ob 和 db/db 小鼠中 GaIN 诱导的炎症性肝损伤，同时巨噬细胞募集以及 IL-12 和 IL-18 的产生显着减少。综上所述，这些结果表明，上调的 OPN 表达是通过促进炎症和调节免疫反应，导致遗传性肥胖小鼠对 GaIN 诱导的肝损伤的易感性增加的一个因素。 (C) 2009 Elsevier Inc. 保留所有权利，
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 (GaIN), 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 GaIN-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 GaIN-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 GaIN-induced liver injury by promoting inflammation and modulating immune response. (C) 2009 Elsevier Inc. All rights reserved,