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

• Material Type: 博士論文
• Title: The differences of collagen XVII between the oral mucosa and the skin discover the pathogenesis of oral lesions in pemphigoid
• Author/Editor: 鎌口, 真由美
• Author Heading: 鎌口, 真由美
• Publication, Distribution, etc.: Hokkaido University
• Publication Date: 2019-03-25
• Publication Date (W3CDTF): 2019-03-25
• Alternative Title: 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
• Contributor: 北川, 善政; 鄭, 漢忠; 樋田, 京子; 岩田, 浩明
• Degree grantor/type: 北海道大学
• Date Granted: 2019-03-25
• Date Granted (W3CDTF): 2019-03-25
• Dissertation Number: 甲第13491号
• Degree Type: 博士(歯学)
• Conferring No. (Dissertation): 甲第13491号
• Text Language Code: eng
• Subject Heading: keratinocyte; collagen XVII; oral mucosa; bullous pemphigoid; depletion
• NDC: 497
• Target Audience: 一般
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11479116; https://dl.ndl.go.jp/pid/11479116
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-04-06T03:04:11+09:00
• Format (IMT): PDF
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.14943/doctoral.k13491; http://hdl.handle.net/2115/76953
• Is Referenced By (URI): http://hdl.handle.net/2115/73981
• Data Provider (Database): 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

• Summary, etc.: The basement membrane zone (BMZ) consists of multiple components, including collagen XVII (COL17), which is the major targeted antigen of pemphigoid d...