Oligosaccharide modification by N‐acetylglucosaminyltransferase‐V in macrophages are involved in pathogenesis of bleomycin‐induced scleroderma. Issue 8 (26th May 2015)

• Record Type: Journal Article
• Authors: Kato, Arisa; Yutani, Mizuki; Terao, Mika; Kimura, Akihiro; Itoi, Saori; Murota, Hiroyuki; Miyoshi, Eiji; Katayama, Ichiro
• Is Part Of: Experimental dermatology. Volume 24:Issue 8(2015:Aug.)
• Page Start: 585
• Page End: 590
• Publication Date: 2015-05-26
• Subjects: Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.12730
• Languages: English
• ISSNs: 0906-6705

Abstract

<abstract abstract-type="main" id="exd12730-abs-0001"> <title>Abstract</title> <p>Oligosaccharide modification by <italic>N</italic>‐acetylglucosaminyltransferase‐V (GnT‐V), which catalyses the formation of <italic>β</italic>1, 6 GlcNAc (N‐acetylglucosamine) branches on <italic>N</italic>‐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 (<italic>MGAT5</italic><sup><italic>−/−</italic></sup>) mice. Expression of GnT‐V was also elevated in bleomycin (BLM)‐injected sclerotic skin, and <italic>MGAT5</italic><sup><italic>−/−</italic></sup> mice were resistant to BLM‐induced skin sclerosis with reduced collagen type 1 <italic>α</italic>1 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 <italic>MGAT5</italic><sup><italic>−/−</italic></sup> mice. In bone marrow‐derived macrophages (BMDMs), IL‐4‐induced expressions of Fizz1 and Ym1 were significantly reduced in <italic>MGAT5</italic><sup><italic>−/−</italic></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.</p> </abstract>