The differences of collagen XVII between the oral mucosa and the skin discover the pathogenesis of oral lesions in pemphigoid

• 資料種別: 博士論文
• タイトル: The differences of collagen XVII between the oral mucosa and the skin discover the pathogenesis of oral lesions in pemphigoid
• 著者・編者: 鎌口, 真由美
• 著者標目: 鎌口, 真由美
• 出版事項: Hokkaido University
• 出版年月日等: 2019-03-25
• 出版年（W3CDTF）: 2019-03-25
• 並列タイトル等: 17型コラーゲンに着目した類天疱瘡における口腔内水疱形成機序の解明
• 寄与者: 北川, 善政; 鄭, 漢忠; 樋田, 京子; 岩田, 浩明
• 授与機関名: 北海道大学
• 授与年月日: 2019-03-25
• 授与年月日（W3CDTF）: 2019-03-25
• 報告番号: 甲第13491号
• 学位: 博士(歯学)
• 博論授与番号: 甲第13491号
• 本文の言語コード: eng
• 件名標目: keratinocyte; collagen XVII; oral mucosa; bullous pemphigoid; depletion
• NDC: 497
• 対象利用者: 一般
• 一般注記: The basement membrane zone (BMZ) consists of multiple components, including collagen XVII (COL17), which is the major targeted antigen of pemphigoid diseases such as bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). The blistering mechanisms in pemphigoid have not been fully elucidated, especially in MMP, which mainly affects the mucosa. No research has addressed the differences in BMZ components between the skin and the oral mucosa. In this study, we investigate the differences of BMZ proteins especially COL17 between the skin and the oral mucosa to elucidate the pathogenesis of oral lesion in pemphigoid. We showed that the MMP sera react preferentially to the oral mucosal substrates than the skin substrates. As well as the diversity of the reactivity of MMP autoantibodies, it was suggested that there are certain differences between the skin and the oral mucosa as autoantigens itself. We found that the expression levels of COL17 were significantly higher in normal human oral mucosal keratinocytes (NHOMKs) than in normal human epidermal keratinocytes (NHEKs). The high expression levels of COL17 compensate for COL17-depletion induced by pemphigoid IgG. These results may influence the clinical differences in pemphigoid. Furthermore, using immunoprecipitation, we revealed that COL17 directly binds to collagen IV (COL4) in NHEKs and NHOMKs. In particular, the C-terminus of COL17 is binding site to COL4 in NHOMKs. MMP-IgG or monoclonal antibody recognizing the C-terminus hindered the interaction of COL17 with COL4 in NHOMKs. These results are clinically relevant to less inflammatory phenotype in MMP. The inflammatory infiltrates around perilesions were significantly less in MMP compared to BP. These results indicate that pemphigoid IgG targeting the C-terminus plays a pathogenic role in blister formation in the oral mucosa to inhibit protein interactions with less inflammation.; (主査) 教授 北川 善政, 教授 鄭 漢忠, 教授 樋田 京子, 診療講師 岩田 浩明（医学研究院）; 歯学研究科(口腔医学専攻)
• DOI: 10.14943/doctoral.k13491; https://doi.org/10.14943/doctoral.k13491
• 国立国会図書館永続的識別子: info:ndljp/pid/11479116; https://dl.ndl.go.jp/pid/11479116
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2020-04-06T03:04:11+09:00
• 記録形式（IMT）: PDF
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://dx.doi.org/10.14943/doctoral.k13491; http://hdl.handle.net/2115/76953
• 参照（URI）: http://hdl.handle.net/2115/73981
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp