PMID- 25876794 OWN - NLM STAT- MEDLINE DCOM- 20160517 LR - 20211203 IS - 1600-0625 (Electronic) IS - 0906-6705 (Linking) VI - 24 IP - 8 DP - 2015 Aug TI - Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma. PG - 585-90 LID - 10.1111/exd.12730 [doi] AB - Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), which catalyses the formation of beta1,6 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 alpha1 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. CI - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Kato, Arisa AU - Kato A AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. AD - Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Yutani, Mizuki AU - Yutani M AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. AD - Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Terao, Mika AU - Terao M AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Kimura, Akihiro AU - Kimura A AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. AD - Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Itoi, Saori AU - Itoi S AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Murota, Hiroyuki AU - Murota H AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Miyoshi, Eiji AU - Miyoshi E AD - Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Katayama, Ichiro AU - Katayama I AD - Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150526 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (CD3 Complex) RN - 0 (Collagen Type I) RN - 0 (Collagen Type I, alpha 1 Chain) RN - 0 (Cytokines) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lectins) RN - 0 (Receptors, Cell Surface) RN - 0 (Retnla protein, mouse) RN - 11056-06-7 (Bleomycin) RN - 207137-56-2 (Interleukin-4) RN - EC 2.4.1.- (Mgat5 protein, human) RN - EC 2.4.1.- (N-Acetylglucosaminyltransferases) RN - EC 2.4.1.155 (alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase) RN - EC 3.2.1.52 (Chil3 protein, mouse) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) SB - IM CIN - Exp Dermatol. 2015 Aug;24(8):576-8. PMID: 25869115 MH - Animals MH - Antigens, CD/analysis MH - Antigens, Differentiation, Myelomonocytic/analysis MH - Bleomycin/*toxicity MH - CD3 Complex/analysis MH - Collagen Type I/deficiency MH - Collagen Type I, alpha 1 Chain MH - Cytokines/pharmacology MH - Humans MH - Intercellular Signaling Peptides and Proteins/biosynthesis/genetics MH - Interleukin-4/pharmacology MH - Lectins/biosynthesis/genetics MH - Macrophages/chemistry/drug effects/enzymology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - N-Acetylglucosaminyltransferases/deficiency/genetics/*physiology MH - Receptors, Cell Surface/analysis MH - Scleroderma, Systemic/chemically induced/*enzymology/pathology MH - Sclerosis MH - Skin/enzymology/pathology MH - T-Lymphocyte Subsets/chemistry/enzymology MH - beta-N-Acetylhexosaminidases/biosynthesis/genetics OTO - NOTNLM OT - N-acetylglucosaminyltransferase-V OT - bleomycin OT - localized scleroderma OT - macrophages OT - systemic sclerosis EDAT- 2015/04/17 06:00 MHDA- 2016/05/18 06:00 CRDT- 2015/04/17 06:00 PHST- 2015/04/08 00:00 [accepted] PHST- 2015/04/17 06:00 [entrez] PHST- 2015/04/17 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] AID - 10.1111/exd.12730 [doi] PST - ppublish SO - Exp Dermatol. 2015 Aug;24(8):585-90. doi: 10.1111/exd.12730. Epub 2015 May 26.