Elucidation of epigenetic mechanism required for chronic inflammatory phenotype in conjunctival fibroblasts derived from severe allergic conjunctivitis
Project/Area Number |
17K11500
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | Nihon Pharmaceutical University (2018-2019) National Center for Child Health and Development (2017) |
Principal Investigator |
OKADA NAOKO 日本薬科大学, 薬学部, 助教 (50636165)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | エピジェネティクス / ペリオスチン / 重症アレルギー性結膜炎 / 線維芽細胞 / アレルギー性結膜炎 |
Outline of Final Research Achievements |
Atopic keratoconjunctivitis (AKC) represents severe forms of ocular allergies. It is characterized by chronically relapsing ocular inflammatory diseases that cause intense inflammation and fibrosis in conjunctiva. However, the precise mechanisms by which the diseases are resistant to treatment remains unknown. We previously focused on conjunctival fibroblasts derived from severe ocular allergic conjunctivitis patients and compared the gene expression patterns. It was found that the expression of periostin was significantly enhanced in the conjunctival fibroblasts derived from patients in the unstimulated state, and this expression was maintained even after the subculture. In this study, we found that epigenetic induction by enzymes involved in histone methylation status play an important role in periostin high expression in conjunctival fibroblasts. Furthermore, it was revealed that high expression of periostin in conjunctival fibroblasts can be suppressed by controlling the enzymes.
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Academic Significance and Societal Importance of the Research Achievements |
線維芽細胞はがんや関節リウマチなど様々な慢性炎症疾患において、炎症局所の微小環境中での様々なストレスに応答し、細胞のエピジェネティック変化が誘導されることで、慢性炎症を引き起こすことが数多く報告されている。一方、アレルギー疾患においては、炎症組織中の細胞を採取・評価できる疾患が少なく、検討が進んでいない。本研究では結膜線維芽細胞を用いて、慢性炎症型の表現型獲得とその維持のために重要なエピジェネティクスのメカニズムとその制御法を初めて解明した。またエピジェネティクス制御化合物は、眼アレルギーに限らず、炎症メカニズムが類似した疾患における治癒困難な線維化に対し、新たな治療法となる可能性がある。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid2019
Author(s)
Morita H, Kubo T, Ruckert B, Ravindran A, Soyka M, Rinaldi A, Sugita K, Wawrzyniak M, Wawrzyniak P, Motomura K, Tamari M, Orimo K, Okada N, Arae K, Saito K, Altunbulakli C, Castro-Giner F, Tan G, Neumann A, Sudo K, O’Mahony L, Honda K, Nakae S, Saito H, Mjösberg J, Nilsson G, Matsumoto K, Akdis M, Akdis CA
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Journal Title
J Allergy Clin Immunol.
Volume: in press
Issue: 6
Pages: 2190-2201
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non-eosinophilic chronic rhinosinusitis.2018
Author(s)
Okada N, Nakayama T, Asaka D, Inoue N, Tsurumoto T, Takaishi S, Otori N, Kojima H, Matsuda A, Oboki K, Saito H, Matsumoto K, Yoshikawa M.
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Journal Title
Int Forum Allergy Rhinol.
Volume: 8
Issue: 5
Pages: 592-604
DOI
Related Report
Peer Reviewed
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[Journal Article] A Rho-associated coiled-coil containing kinases (ROCK) inhibitor, Y-27632, enhances adhesion, viability and differentiation of human term placenta-derived trophoblasts in vitro2017
Author(s)
Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, and Kenji Matsumoto
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Journal Title
PLOS ONE
Volume: in press
Issue: 5
Pages: e0177994-e0177994
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Gene expression profiling of acute type A aortic dissection combined with in vitro assessment.2017
Author(s)
Kimura N, Futamura K, Arakawa M, Okada N, Emrich F, Okamura H, Sato T, Shudo Y, Koyano TK, Yamaguchi A, Adachi H, Matsuda A, Kawahito K, Matsumoto K, Fischbein MP.
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Journal Title
European Journal of Cardio-Thoracic Surgery
Volume: 52
Issue: 4
Pages: 810-817
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Human eosinophils constitutively express a unique serine protease, PRSS332017
Author(s)
Toyama S, Okada N, Matsuda A, Morita H, Saito H, Fujisawa T, Nakae S, Karasuyama H, Matsumoto K.
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Journal Title
Allergology International
Volume: 66
Issue: 3
Pages: 463-471
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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