title: Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma.
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(+) M2 macrophages. To determine the role of GnT-V in scleroderma, we next investigated skin sclerosis in GnT-V knockout (MGAT5(-/-) ) mice. Expression of GnT-V was also elevated in bleomycin (BLM)-injected sclerotic skin, and MGAT5(-/-) 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(+) M2 macrophages and CD3-positive T cells in BLM-induced skin sclerosis was significantly fewer in MGAT5(-/-) mice. In bone marrow-derived macrophages (BMDMs), IL-4-induced expressions of Fizz1 and Ym1 were significantly reduced in MGAT5(-/-) 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.
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Arisa
authors: A
authors: Kato
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Mizuki
authors: M
authors: Yutani
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Mika
authors: M
authors: Terao
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Akihiro
authors: A
authors: Kimura
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Saori
authors: S
authors: Itoi
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Hiroyuki
authors: H
authors: Murota
authors: Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Eiji
authors: E
authors: Miyoshi
authors: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Ichiro
authors: I
authors: Katayama
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001761:Bleomycin / Q000633:toxicity*; D017252:CD3 Complex / Q000032:analysis; D024042:Collagen Type I / Q000172:deficiency; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D037102:Lectins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D012598:Sclerosis; D012867:Skin / Q000201:enzymology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D017252:CD3 Complex; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D011956:Receptors, Cell Surface; C413576:Retnla protein, mouse; D001761:Bleomycin; D015847:Interleukin-4; C000601122:Mgat5 protein, human; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases
keywords: N-acetylglucosaminyltransferase-V; bleomycin; localized scleroderma; macrophages; systemic sclerosis