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The differences of collagen XVII between the oral mucosa and the skin discover the pathogenesis of oral lesions in pemphigoid
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| Title: | The differences of collagen XVII between the oral mucosa and the skin discover the pathogenesis of oral lesions in pemphigoid |
| Other Titles: | 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 |
| Authors: | 鎌口, 真由美 Browse this author |
| Keywords: | keratinocyte | | collagen XVII | | oral mucosa | | bullous pemphigoid | | depletion |
| Issue Date: | 25-Mar-2019 |
| Publisher: | Hokkaido University |
| Abstract: | 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. |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第13491号 |
| Degree Level: | 博士 |
| Degree Discipline: | 歯学 |
| Examination Committee Members: | (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） |
| Degree Affiliation: | 歯学研究科(口腔医学専攻) |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/76953 |
| Appears in Collections: | 課程博士 (Doctorate by way of Advanced Course) > 歯学院(Graduate School of Dental Medicine)
学位論文 (Theses) > 博士 （歯学）
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