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Article

N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice

  • Authors:
    • Yoshihiro Kamada
    • Motoya Sato
    • Sachiho Kida
    • Maaya Akita
    • Kayo  Mizutani
    • Hironobu Fujii
    • Tomoaki Sobajima
    • Yuichi Yoshida
    • Shinichiro  Shinzaki
    • Shinji Takamatsu
    • Tetsuo Takehara
    • Eiji Miyoshi
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan
  • Pages: 3573-3584
    |
    Published online on: January 8, 2015
       https://doi.org/10.3892/mmr.2015.3168
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Abstract

N‑Acetylglucosaminyltransferase V (GnT‑V) catalyzes β1‑6 branching in asparagine‑linked oligosaccharides and is one of the most important glycosyltransferases involved in carcinogenesis, cancer metastasis and immunity. To investigate the biological functions of GnT‑V, the present study developed GnT‑V transgenic (Tg) mice and the role of GnT‑V in experimental immune‑mediated hepatitis, induced by concanavalin A (ConA), were investigated. It was found that the aberrant expression of GnT‑V exacerbated ConA‑induced hepatitis in the Tg mice compared with the wild‑type (WT) mice. The survival rate of the ConA‑induced hepatitis at a high‑dose of ConA was significantly lower in the Tg mice. Intravenously injected ConA is known to initially bind predominantly to the mannose gland of the liver sinusoidal endothelial cell (LSEC) surface and to leads to the activation of various immune cells. In the present study, the binding affinity of ConA to the LSECs did not differ between the WT and Tg mice. In addition, T cell receptor stimulation by anti‑cluster of differentiation (CD)3/CD28 antibodies produced lower levels of T helper (Th)1 cytokine (interferon‑γ) and higher levels of Th2 cytokine (interleukin‑10) in the Tg mouse splenic lymphocytes compared with WT mice. The composition of the hepatic mononuclear cells revealed that CD11b‑positive cells were significantly increased in the GnT‑V Tg mice. In addition, F4/80‑positive cells were significantly increased in the Tg mouse liver and the depletion of macrophages reduced the difference in the severity of ConA‑induced hepatitis between the WT and Tg mice. In conclusion, the present findings indicated that the aberrant expression of GnT‑V led to an increase in hepatic macrophage infiltration and enhanced ConA‑induced hepatitis. Modulation of glycosylation may be a novel therapeutic target for immunity‑associated acute hepatitis.
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Copy and paste a formatted citation
Spandidos Publications style
Kamada Y, Sato M, Kida S, Akita M, Mizutani K, Fujii H, Sobajima T, Yoshida Y, Shinzaki S, Takamatsu S, Takamatsu S, et al: N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice. Mol Med Rep 11: 3573-3584, 2015.
APA
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H. ... Miyoshi, E. (2015). N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice. Molecular Medicine Reports, 11, 3573-3584. https://doi.org/10.3892/mmr.2015.3168
MLA
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H., Sobajima, T., Yoshida, Y., Shinzaki, S., Takamatsu, S., Takehara, T., Miyoshi, E."N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice". Molecular Medicine Reports 11.5 (2015): 3573-3584.
Chicago
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H., Sobajima, T., Yoshida, Y., Shinzaki, S., Takamatsu, S., Takehara, T., Miyoshi, E."N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice". Molecular Medicine Reports 11, no. 5 (2015): 3573-3584. https://doi.org/10.3892/mmr.2015.3168
Copy and paste a formatted citation
x
Spandidos Publications style
Kamada Y, Sato M, Kida S, Akita M, Mizutani K, Fujii H, Sobajima T, Yoshida Y, Shinzaki S, Takamatsu S, Takamatsu S, et al: N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice. Mol Med Rep 11: 3573-3584, 2015.
APA
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H. ... Miyoshi, E. (2015). N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice. Molecular Medicine Reports, 11, 3573-3584. https://doi.org/10.3892/mmr.2015.3168
MLA
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H., Sobajima, T., Yoshida, Y., Shinzaki, S., Takamatsu, S., Takehara, T., Miyoshi, E."N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice". Molecular Medicine Reports 11.5 (2015): 3573-3584.
Chicago
Kamada, Y., Sato, M., Kida, S., Akita, M., Mizutani, K., Fujii, H., Sobajima, T., Yoshida, Y., Shinzaki, S., Takamatsu, S., Takehara, T., Miyoshi, E."N‑Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice". Molecular Medicine Reports 11, no. 5 (2015): 3573-3584. https://doi.org/10.3892/mmr.2015.3168
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