Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma

Arisa Kato, Mizuki Yutani, Mika Terao, Akihiro Kimura, Saori Itoi, Hiroyuki Murota, Eiji Miyoshi, Ichiro Katayama

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), which catalyses the formation of β1,6 GlcNAc (N-acetylglucosamine) branches on N-glycans, is associated with various pathologies, such as cancer metastasis, multiple sclerosis and liver fibrosis. In this study, we demonstrated the involvement of GnT-V in the pathophysiology of scleroderma. High expression of GnT-V was observed in infiltrating cells in skin section samples from systemic and localized patients with scleroderma. Most of the infiltrating cells were T cells and macrophages, most of which were CD163<sup>+</sup> M2 macrophages. To determine the role of GnT-V in scleroderma, we next investigated skin sclerosis in GnT-V knockout (MGAT5<sup>-/-</sup>) mice. Expression of GnT-V was also elevated in bleomycin (BLM)-injected sclerotic skin, and MGAT5<sup>-/-</sup> mice were resistant to BLM-induced skin sclerosis with reduced collagen type 1 α1 content, suggesting the biological significance of GnT-V in skin sclerosis. Furthermore, the number of CD163<sup>+</sup> M2 macrophages and CD3-positive T cells in BLM-induced skin sclerosis was significantly fewer in MGAT5<sup>-/-</sup> mice. In bone marrow-derived macrophages (BMDMs), IL-4-induced expressions of Fizz1 and Ym1 were significantly reduced in MGAT5<sup>-/-</sup> mice-derived BMDMs. Taken together, these results suggest the induction of GnT-V in skin sclerosis progression is possibly dependent on increased numbers of M2 macrophages in the skin, which are important for tissue fibrosis and remodelling.

Original languageEnglish
JournalExperimental Dermatology
DOIs
Publication statusAccepted/In press - 2015

Keywords

  • Bleomycin
  • Localized scleroderma
  • Macrophages
  • N-acetylglucosaminyltransferase-V
  • Systemic sclerosis

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

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