Development of the novel diagnostic method on mucous membrane pemphigoid using saliva

• Project/Area Number: 16K20585
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: YASUKOCHI Atsushi 九州大学, 歯学研究院, 共同研究員 (30724968)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 粘膜類天疱瘡 / BP180 / 口腔癌 / 歯学

Outline of Final Research Achievements

This project focused on BP180 as one of the autoantibody target antigens of the pemphigoid group and analyzed regulation mechanism of its expression. In the course of analysis, it was found that the basement membrane structure dissociation in pemphigoid was similar to that seen in cancer invasion.
Therefore, we further analyzed expression control of BP180 in oral cancer (gingival and tongue cancer) cells and tissue samples compared with normal tongue tissue, and we have identified that miR-203 is involved in p53-independent control of BP180 expression. Furthermore, the interaction among BP180, wild-type p53, mutant p53, and miR203 was analyzed in vitro (Yasukochi A et al., J Biochem, 2019)

Academic Significance and Societal Importance of the Research Achievements

類天疱瘡群は、表皮真皮間結合部の接着機構であるヘミデスモソームを構成する分子に対する自己抗体が生じることにより表皮下水疱を生じる自己免疫性水疱症疾患であるが、その自己抗体の標的抗原は多彩であり、具体的な疾患発症に関わる責任抗原は明確となっていない。病態解明に結びつくBP180の機能解析の進捗が滞っている理由に、BP180の発現制御機構やそのリガンドが解明されていないことが挙げられる。
本研究によって明らかとなった、新規のBP180発現制御機構は、ヘミデスモソームの解離が病態の主体である類天疱瘡のほか、癌浸潤機構や創傷治癒機転の解明にもつながり、様々な疾患に対する新たな治療標的を提示した。

Research Products

• [Journal Article] Regulation of collagen type XVII expression by miR203a-3p in oral squamous cell carcinoma cells (2019)
  • Author(s): Yasukochi A, Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Nishinakagawa T, Ono K, Nakashima M, Nakamura S.
  • Journal Title: J Biochem Volume: in press Issue: 2 Pages: 163-173
  • DOI: 10.1093/jb/mvz024
  • Peer Reviewed
• [Journal Article] miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment. (2018)
  • Author(s): Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Yasukochi A, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
  • Journal Title: Mol Carcinog Volume: 57 Issue: 2 Pages: 295-302
  • DOI: 10.1002/mc.22744
  • NAID: 120006900039
  • Peer Reviewed / Open Access
• [Journal Article] Clinical and Immunological Study of 332 Japanese Patients Tentatively Diagnosed with Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay. (2016)
  • Author(s): Yasukochi A, Teye K, Ishii N, Hashimoto T.
  • Journal Title: Acta Derm Venereol. Volume: 0 Pages: 0-0
  • DOI: 10.2340/00015555-2407
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Granular C3 Dermatosis. (2016)
  • Author(s): Hashimoto T, Tsuruta D, Yasukochi A, Imanishi H, Sekine H, Fujita T, Wanibuchi H, Gi M, Kárpáti S, Sitaru C, Zone JJ, Endo D, Abe S, Nishino T, Koji T, Ishii N.
  • Journal Title: Acta Derm Venereol Volume: 00 Pages: 00-00
  • DOI: 10.2340/00015555-2379
  • NAID: 120006987674
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] miR-200c-3pによる口腔扁平上皮癌の浸潤制御機構 (2019)
  • Author(s): 安河内（川久保）友世、森岡政彦、櫨川舞、西中川拓也、安河内篤、中村誠司、中島学
  • Organizer: 第92回日本薬理学会年会
• [Presentation] The significance of BP180 expression in oral squamous carcinoma cell invasion (2017)
  • Author(s): Yasukochi A, Morioka M, Kawakubo-Yasukochi T, Nakashima M, Nakamura S
  • Organizer: The 5th Congress of ASHNO
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2017-03-23
  • Int'l Joint Research
• [Presentation] 口腔扁平上皮癌における BP180 の局在 (2017)
  • Author(s): 安河内篤、森岡政彦、川久保－安河内友世、中島 学、中村 誠司
  • Organizer: 第５９回歯科基礎医学会学術大会
• [Presentation] 非コードRNAによる口腔癌の進展抑制 (2017)
  • Author(s): 川久保－安河内友世、森岡政彦、安河内篤、中村 誠司、中島 学
  • Organizer: 第５９回歯科基礎医学会学術大会
• [Presentation] Link of BP180 bullous pemphigoid autoantigen to invasion of oral squamous carcinoma cell (2016)
  • Author(s): Yasukochi A, Morioka M, Kawakubo-Yasukochi T, Obayashi K, Nakashima M, Nakamura S
  • Organizer: ANZHNCS Annual Scientific Meeting and the IFHNOS 2016 World Tour
  • Place of Presentation: Auckland, New Zealand
  • Year and Date: 2016-10-25
  • Int'l Joint Research