Fatty acid binding protein 7 regulates phagocytosis and cytokine production in kupffer cells during liver injury

Hirofumi Miyazaki, Tomoo Sawada, Miwa Kiyohira, Zhiqian Yu, Keiji Nakamura, Yuki Yasumoto, Yoshiteru Kagawa, Majid Ebrahimi, Ariful Islam, Kazem Sharifi, Saki Kawamura, Takanori Kodama, Yui Yamamoto, Yasuhiro Adachi, Nobuko Tokuda, Shuji Terai, Isao Sakaida, Toshizo Ishikawa, Yuji Owada

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2505-2515
Number of pages11
JournalAmerican Journal of Pathology
Volume184
Issue number9
DOIs
Publication statusPublished - 2014 Sep

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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