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

Journal Article · Mon Feb 01 04:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.006· OSTI ID:21344857

Kwon, Hyo-Jung ^[1]; Won, Young-Suk; Yoon, Won-Kee; Nam, Ki-Hoan ^[1]; Kim, Dae-Yong ^[2]; Kim, Hyoung-Chin ^[1]

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1. Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk (Korea, Republic of)
2. Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of)

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.

• OSTI ID: 21344857
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 242; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
BODY
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
DOSES
ENZYMES
GLANDS
GROWTH FACTORS
HAZARDS
HISTOLOGY
INFLAMMATION
INJURIES
LIVER
LIVER CELLS
LYMPHOKINES
MACROPHAGES
MAMMALS
METABOLIC DISEASES
MICE
MITOGENS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHAGOCYTES
PROTEINS
RODENTS
SOMATIC CELLS
SYMPTOMS
VERTEBRATES