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DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins
IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998650/ https://www.ncbi.nlm.nih.gov/pubmed/26886650 http://dx.doi.org/10.1097/MD.0000000000002853 |
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author | Ohta, Miho Moriyama, Masafumi Maehara, Takashi Gion, Yuka Furukawa, Sachiko Tanaka, Akihiko Hayashida, Jun-Nosuke Yamauchi, Masaki Ishiguro, Noriko Mikami, Yurie Tsuboi, Hiroto Iizuka-Koga, Mana Kawano, Shintaro Sato, Yasuharu Kiyoshima, Tamotsu Sumida, Takayuki Nakamura, Seiji |
author_facet | Ohta, Miho Moriyama, Masafumi Maehara, Takashi Gion, Yuka Furukawa, Sachiko Tanaka, Akihiko Hayashida, Jun-Nosuke Yamauchi, Masaki Ishiguro, Noriko Mikami, Yurie Tsuboi, Hiroto Iizuka-Koga, Mana Kawano, Shintaro Sato, Yasuharu Kiyoshima, Tamotsu Sumida, Takayuki Nakamura, Seiji |
author_sort | Ohta, Miho |
collection | PubMed |
description | IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjögren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO. |
format | Online Article Text |
id | pubmed-4998650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-49986502016-09-06 DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins Ohta, Miho Moriyama, Masafumi Maehara, Takashi Gion, Yuka Furukawa, Sachiko Tanaka, Akihiko Hayashida, Jun-Nosuke Yamauchi, Masaki Ishiguro, Noriko Mikami, Yurie Tsuboi, Hiroto Iizuka-Koga, Mana Kawano, Shintaro Sato, Yasuharu Kiyoshima, Tamotsu Sumida, Takayuki Nakamura, Seiji Medicine (Baltimore) 3600 IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjögren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO. Wolters Kluwer Health 2016-02-18 /pmc/articles/PMC4998650/ /pubmed/26886650 http://dx.doi.org/10.1097/MD.0000000000002853 Text en Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 |
spellingShingle | 3600 Ohta, Miho Moriyama, Masafumi Maehara, Takashi Gion, Yuka Furukawa, Sachiko Tanaka, Akihiko Hayashida, Jun-Nosuke Yamauchi, Masaki Ishiguro, Noriko Mikami, Yurie Tsuboi, Hiroto Iizuka-Koga, Mana Kawano, Shintaro Sato, Yasuharu Kiyoshima, Tamotsu Sumida, Takayuki Nakamura, Seiji DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title | DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title_full | DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title_fullStr | DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title_full_unstemmed | DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title_short | DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins |
title_sort | dna microarray analysis of submandibular glands in igg4-related disease indicates a role for marco and other innate immune-related proteins |
topic | 3600 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998650/ https://www.ncbi.nlm.nih.gov/pubmed/26886650 http://dx.doi.org/10.1097/MD.0000000000002853 |
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