title: Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury.
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.
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Kiyohira
authors.affiliation: Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasumoto
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Majid
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Ariful
authors.initials: A
authors.lastname: Islam
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Kazem
authors.initials: K
authors.lastname: Sharifi
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Kawamura
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Adachi
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan; Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Tokuda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.affiliation: Division of Neurosciences, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Toshizo
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan. Electronic address: yowada@yamaguchi-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009419:Nerve Tissue Proteins; D002251:Carbon Tetrachloride