The role of miRNA in airway epitherial cells

• Project/Area Number: 15K19439
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Igarashi Arisa 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 (60572998)
• Research Collaborator: OKAMURA Kohji ; MATSUDA Akio ; MATSUMOTO Kenji
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: microRNA / 上皮細胞 / 喘息 / miR-29 / sST2 / IL33 / miRNA / アレルギー / 自然免疫 / ぜんそく

Outline of Final Research Achievements

To identify miRNAs that regulate expression of IL-33, an important cytokine gene for asthma development, expression of miRNAs in human airway epithelial cells was investigated. Consequently, although a novel miRNA directly controlling IL-33 expression could not be identified, miR-29 was found to regulate epithelial expression of both soluble ST2 (sST2), a decoy receptor for IL-33, and IFNAR1, a type 1 interferon receptor. Furthermore, I found that miR-29 is produced extracellularly via exosomes secreted by airway epithelial cells.
These results suggest that miR-29 may be involved in the IL-33-dependent molecular mechanisms of asthma development, triggered by respiratory viral infection, via regulation of sST2 and IFNAR1 expression in the airway epithelial cells.

Research Products

• [Journal Article] Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses (2017)
  • Author(s): M. Sakaki, Y. Ebihara, K. Okamura, K. Nakabayashi, A. Igarashi, K. Matsumoto, K. Hata, Y. Kobayashi, and K. Maehara
  • Journal Title: PLOS ONE Volume: 12(2) Issue: 2 Pages: e0171431-e0171431
  • DOI: 10.1371/journal.pone.0171431
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of targets of tumor suppressor microRNA-34a using a reporter library system. (2017)
  • Author(s): Ito Y, Inoue A, Seers T, Hato Y, Igarashi A, Toyama T, Taganov KD, Boldin MP, Asahara H.
  • Journal Title: Proc Natl Acad Sci USA Volume: - Issue: 15 Pages: 3927-3932
  • DOI: 10.1073/pnas.1620019114
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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
• [Journal Article] Conditional deletion of CD98hc inhibits osteoclast development. (2016)
  • Author(s): Tsumura H, Ito M, Takami M, Arai M, Li XK, Hamatani T, Igarashi A, Takada S, Miyado K, Umezawa A, Ito Y.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 5 Pages: 203-210
  • DOI: 10.1016/j.bbrep.2015.11.023
  • Peer Reviewed
• [Journal Article] Lack of Skeletal Dysplasia in Patients with Missense Mutations and Upstream Deletion of SOX9. (2015)
  • Author(s): Katoh-Fukui Y, Igarashi M, Nagasaki K, Horikawa R, Nagai T, Tsuchiya T, Suzuki E, Miyado M, Hata K, Nakabayashi K, Hayashi K, Matsubara Y, Baba T, Morohashi K, Igarashi A, Ogata T, Takada S, and Fukami M
  • Journal Title: Molecular Genetics & Genomic Medicine Volume: 3 Issue: 6 Pages: 550-557
  • DOI: 10.1002/mgg3.165
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] MicroRNA-29 suppresses cytokine-mediated production of soluble IL-33 receptor, sST2, by bronchial epithelial cells (2018)
  • Author(s): Arisa Igarashi, Akio Matsuda, Kenji Matsumoto
  • Organizer: AAAAI/WAO Joint Congress 2018
  • Int'l Joint Research
• [Presentation] MicroRNA-29は気道上皮細胞のIFNAR1発現およびsST2産生を抑制する (2018)
  • Author(s): 五十嵐ありさ 松田明生 松本健治
  • Organizer: 第67回日本アレルギー学会学術大会