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Article

N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium

  • Authors:
    • Huo-Mei Yang
    • Chao Yu
    • Zhu Yang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing 400010, P.R. China, Institute of Life Sciences, Chongqing Medical University, Chongqing, Chongqing 400016, P.R. China
  • Pages: 589-598
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    Published online on: May 17, 2012
       https://doi.org/10.3892/ijo.2012.1484
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Abstract

Changes in the expression of glycosyltransferases that branch N-linked glycans are associated with many physiological and pathological events, such as cell adhesion, migration, proliferation and tumor cell malignancy. Here, the altered levels of N-acetylglucosaminyltransferase V (GnT-V) and its product β(1,6)-linked GlcNAc in monocytes were observed during inflammation. The effects of GnT-V and aberrant N-linked β(1,6) branching on monocyte adhesion through vascular endothelium and transmigration were investigated. During IFN-γ-induced inflammation, adhesion and transendothelial migration of THP-1 monocytes were enhanced, and the levels of GnT-V and β(1,6)-linked GlcNAc in THP-1 monocytes were significantly decreased. Expression of the GnT-V shRNA vector in THP-1 cells reversed the abnormal IFN-γ-induced characteristics, indicating direct involvement of N-glycosylation in these biological effects. The enhanced adhesion and transendothelial migration were significantly inhibited by functional blockade with antibodies against integrin α5 or β1 in IFN-γ-induced and GnT-V knockdown THP-1 cells, demonstrating the involvement of integrin α5β1 in the monocyte-endothelium interaction. However, IFN-γ treatment and GnT-V knockdown in THP-1 cells lowered expression of N-linked β(1,6) branching on integrin α5 and β1, without affecting the total protein expression of the subunits. Decreased GnT-V expression caused marked enchancement of integrin-induced phosphorylation of focal adhesion kinase (FAK). The augmented FAK-mediated ERK phosphorylation and activation were observed in IFN-γ-induced THP-1 cells. Furthermore, ERK inhibitor pre-treatment nearly abrogated the highly elevated IFN-γ-induced monocyte adhesion and transmigration, concomitant with reversal of the decrease in GnT-V and β(1,6) branching. Our results demonstrate for the first time that decreased GnT-V activity due to inflammatory cytokine induction in human monocytes resulted in enchancement of integrin α5β1-dependent monocyte-vascular endothelium adhesion and transmigration. Consequently, the activation of integrin caused elevation of FAK phosphorylation. These effects promoted FAK-mediated downstream signaling, including the ERK pathway, and indicate that GnT-V may be a potential therapeutic target for vascular inflammatory conditions.
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Copy and paste a formatted citation
Spandidos Publications style
Yang H, Yu C and Yang Z: N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium. Int J Oncol 41: 589-598, 2012.
APA
Yang, H., Yu, C., & Yang, Z. (2012). N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium. International Journal of Oncology, 41, 589-598. https://doi.org/10.3892/ijo.2012.1484
MLA
Yang, H., Yu, C., Yang, Z."N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium". International Journal of Oncology 41.2 (2012): 589-598.
Chicago
Yang, H., Yu, C., Yang, Z."N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium". International Journal of Oncology 41, no. 2 (2012): 589-598. https://doi.org/10.3892/ijo.2012.1484
Copy and paste a formatted citation
x
Spandidos Publications style
Yang H, Yu C and Yang Z: N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium. Int J Oncol 41: 589-598, 2012.
APA
Yang, H., Yu, C., & Yang, Z. (2012). N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium. International Journal of Oncology, 41, 589-598. https://doi.org/10.3892/ijo.2012.1484
MLA
Yang, H., Yu, C., Yang, Z."N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium". International Journal of Oncology 41.2 (2012): 589-598.
Chicago
Yang, H., Yu, C., Yang, Z."N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium". International Journal of Oncology 41, no. 2 (2012): 589-598. https://doi.org/10.3892/ijo.2012.1484
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