Identification of constitutive expression mechanism of periostin in conjunctival fibroblasts derived from severe ocular allergic conjunctivitis patients

• Project/Area Number: 15K20296
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: OKADA NAOKO 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, (非)研究員 (50636165)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アレルギー性結膜炎 / 線維芽細胞 / エピジェネティクス / ペリオスチン / 慢性炎症

Outline of Final Research Achievements

Atopic keratoconjunctivitis are severe, chronically relapsing, ocular inflammatory diseases that cause intense inflammation and fibrosis in conjunctiva. However, the precise mechanisms increasing the severity of these diseases remain unknown. We previously focused on conjunctival fibroblasts derived from severe ocular allergic conjunctivitis patients and compared the gene expression patterns. The conjunctival fibroblasts derived from patients showed significantly enhanced periostin expression in the nonstimulated state, and this expression was maintained even after the subculture. In this study, we found that histone methylation state change was occurring at the periostin promoter in patient-derived conjunctival fibroblasts. Furthermore, sustained　periostin expression could observe by TGF-βstimulation. Therefore, these suggested that epigenetic regulation was involved in the induction of long-term and sustained expression of periostin in patient-derived conjunctival fibroblasts.

Research Products

• [Journal Article] Eosinophilic esophagitis versus proton pump inhibitor-responsive esophageal eosinophilia: Transcriptome analysis (2017)
  • Author(s): Shoda T, Matsuda A, Nomura I, Okada N, Orihara K, Mikami H, Ishimura N, Ishihara S, Matsumoto K, Kinoshita Y
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: - Issue: 6 Pages: 2010-2013
  • DOI: 10.1016/j.jaci.2016.11.028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human eosinophils constitutively express a unique serine protease, PRSS33 (2017)
  • Author(s): Toyama S, Okada N, Matsuda A, Morita H, Saito H, Fujisawa T, Nakae S, Karasuyama H, Matsumoto K.
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 463-471
  • DOI: 10.1016/j.alit.2017.01.001
  • NAID: 130005858869
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases. (2016)
  • Author(s): Fujishima H, Okada N, Matsumoto K, Fukagawa K, Igarashi A, Matsuda A, Ono J, Ohta S, Mukai H, Yoshikawa M, Izuhara K.
  • Journal Title: J Allergy Clin Immunol Volume: Epub ahead of print Issue: 2 Pages: 0-0
  • DOI: 10.1016/j.jaci.2015.11.039
  • NAID: 40020962730
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sera of patients with infantile eosinophilic gastroenteritis showed a specific increase in both thymic stromal lymphopoietin and IL-33 levels (2016)
  • Author(s): Shoda T, Matsuda A, Arai K, Shimizu H, Morita H, Orihara K, Okada N, Narita M, Ohya Y, Saito H, Matsumoto K, Nomura I.
  • Journal Title: J Allergy Clin Immunol. Volume: in press Issue: 1 Pages: 299-303
  • DOI: 10.1016/j.jaci.2015.11.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation. (2016)
  • Author(s): Takeda T, Unno H, Morita H, Futamura K, Emi-Sugie M, Arae K, Shoda T, Okada N, Igarashi A, Inoue E, Kitazawa H, Nakae S, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: J Allergy Clin Immunol Volume: In Press Issue: 5 Pages: 1395-1403
  • DOI: 10.1016/j.jaci.2016.01.032
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 重症アレルギー性結膜炎における涙液中へのぺリオスチン産生 (2016)
  • Author(s): 岡田直子、松本健治
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-06-27
• [Presentation] Distinct and common gene expression profiles of nasal polyp tissues in eosinophilic and non-eosinophilic chronic rhinosinusitis. (2016)
  • Author(s): Naoko Okada, Tsuguhisa Nakayama, Daiya Asaka, Akio Matsuda, Hirohisa Saito, Mamoru Yoshikawa, Kenji Matsumoto.
  • Organizer: American Academy of Allergy, Asthma & Immunology.
  • Place of Presentation: Los Angeles, CA
  • Year and Date: 2016-03-04
  • Int'l Joint Research
• [Presentation] Increased periostin levels in tears from patients with allergic ocular diseases. (2015)
  • Author(s): Naoko Okada, Hiroshi Fujishima, Kazumi Fukagawa, Kenji Izuhara, Shoichiro Ohta, Junya Ono, Akio Matsuda, Hirohisa Saito and Kenji Matsumoto.
  • Organizer: European Academy of Allergy and Clinical Immunology.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] アトピー性角結膜炎患者の涙液におけるペリオスチンの発現 (2015)
  • Author(s): 岡田直子、藤島浩、深川和己、松田明生、出原賢治、太田昭一郎、小野純也、斎藤博久、松本健治
  • Organizer: 第27回日本アレルギー学会春季臨床大会
  • Place of Presentation: グランドプリンスホテル新高輪 国際館パミール （東京都港区）
  • Year and Date: 2015-05-26