1. Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury.
- Author
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Miyazaki H, Sawada T, Kiyohira M, Yu Z, Nakamura K, Yasumoto Y, Kagawa Y, Ebrahimi M, Islam A, Sharifi K, Kawamura S, Kodama T, Yamamoto Y, Adachi Y, Tokuda N, Terai S, Sakaida I, Ishikawa T, and Owada Y
- Subjects
- Animals, Blotting, Western, Carbon Tetrachloride toxicity, Chemical and Drug Induced Liver Injury metabolism, Enzyme-Linked Immunosorbent Assay, Fatty Acid-Binding Protein 7, Flow Cytometry, Fluorescent Antibody Technique, Immunohistochemistry, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Chemical and Drug Induced Liver Injury pathology, Cytokines biosynthesis, Fatty Acid-Binding Proteins metabolism, Kupffer Cells metabolism, Nerve Tissue Proteins metabolism, Phagocytosis physiology
- Abstract
Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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