The role of desmosomes and intermediate diameter filament-related factors in the corneal epithelium

• Project/Area Number: 15K10876
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Wakayama Medical University
• Principal Investigator: Kokado Masahide 和歌山県立医科大学, 医学部, 講師 (30445085)
• Co-Investigator(Kenkyū-buntansha): 雑賀 司珠也 和歌山県立医科大学, 医学部, 教授 (40254544) ; 岡田 由香 和歌山県立医科大学, 医学部, 准教授 (50264891)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 創傷治癒 / 角膜上皮 / 角膜創傷治癒

Outline of Final Research Achievements

Knockdown of EPPK with siRNA in cultured corneal epithelial cells suppressed E-cadherin expression and promoted migration and proliferation. The result that down-regulation of EPPK accompanied by down-regulation of E-cadherin expression promoted epithelial cell migration is a common molecular kinetics of epithelial-mesenchymal transition (EMT) of epithelial cells, which is largely related to cancer cell invasion.
Corneal epithelium-specific plakoglobin (JUP) deficient mice were cross created from Cre recombinase-expressing mice and JUP flox/flox mice and reported corneal epithelial fragility and delayed wound healing.

Academic Significance and Societal Importance of the Research Achievements

角膜特異的JUP欠損マウスでの角膜上皮の脆弱性が示されたことから細胞骨格や細胞間接着の障害が想定された。JUP遺伝子異常症例のNaxos病ではNaxos病という，エーゲ海・Naxos島の風土病として知られ，手掌などの角化症とwoolly hairという特徴的な髪の毛の異常を合併する病気があることがギリシャのProtonotarios博士らにより報告されているが、不整脈以外に眼科診療も重要であると考えられた。

Research Products

• [Journal Article] Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice. (2018)
  • Author(s): Kokado M, Miyajima M, Okada Y, Ichikawa K, Yamanaka O, Liu CY, Kao WW, Shou W, Saika S.
  • Journal Title: Laboratory Investigation Volume: 98 Issue: 11 Pages: 1375-1383
  • DOI: 10.1038/s41374-018-0082-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Morphology,wound healing and fragility of corneal epithelium induced by cornea-specific loss of plakoglobin in mice (2017)
  • Author(s): 小門正英
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (国際学会）
  • Place of Presentation: Baltimore,Maryland,USA
  • Year and Date: 2017-05-07
• [Presentation] 角膜上皮特異的プラコグロビン欠失マウスの角膜上皮の脆弱性 (2017)
  • Author(s): 小門正英
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2017-04-06
• [Presentation] Morphology,wound healing and fragility of corneal epithelium induced by cornea-specific loss of plakoglobin in mice. (2017)
  • Author(s): 6．Kokado M, Miyajima M, Okada Y, Yamanaka O, Liu CY, Kao WW, Shou W, Saika S.
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Int'l Joint Research
• [Presentation] 角膜上皮特異的プラコグロビン欠失マウスの作成とその角膜上皮の構造 (2016)
  • Author(s): 小門正英
  • Organizer: 日本結合織学会学術大会
  • Place of Presentation: 長崎市
  • Year and Date: 2016-06-24
• [Presentation] 角膜上皮特異的プラコグロビン欠失マウスの作成とその角膜上皮の構造 (2016)
  • Author(s): 小門正英
  • Organizer: 日本結合組織学会学術大会
  • Place of Presentation: 長崎市
  • Year and Date: 2016-06-24
• [Presentation] Phenotype of corenal epithelium-specific deletion of plakoglobin in mice; morphology and wound healing (2016)
  • Author(s): 小門正英
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (国際学会）
  • Place of Presentation: Seattle,WA,USA
  • Year and Date: 2016-05-01
• [Presentation] Phenotype of corenal epithelium-specific deletion of plakoglobin in mice; morphology and wound healing (2016)
  • Author(s): 小門正英
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Seattle,WA,USA
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] 角膜上皮特異的プラコグロビン欠失マウスのその角膜上皮の構造 (2016)
  • Author(s): 小門正英
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-04
• [Presentation] 角膜上皮特異的プラコグロビン欠失マウスの作成とその角膜上皮の構造 (2016)
  • Author(s): 小門正英
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-04