The importance of thioredoxin in the neonatal chronic lung disease

• Project/Area Number: 17K18156
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine; Pediatrics
• Research Institution: Nihon University
• Principal Investigator: NAGANO Nobuhiko 日本大学, 医学部, 准教授 (90794701)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: チオレドキシン / 新生児慢性肺障害 / 新生仔マウス / 高濃度酸素暴露 / 肺胞発達遅延の抑制 / 炎症性マーカーの上昇抑制 / マクロファージの遊走抑制 / バイオマーカー / 早産児 / 血清TRX-1

Outline of Final Research Achievements

We investigated thioredoxin-1 (TRX) impact on hyperoxic lung injury in newborn TRX transgenic (TRX-Tg) and wildtype (WT) mice exposed to 21% or 95% O2 for four days, after which some mice were allowed to recover in room air for up to 14 days. Lung morphology was assessed by hematoxylin/eosin and elastin staining, as well as immunostaining for macrophages. The gene expression levels of proinflammatory cyrtokines were evaluated using quantitative real-time polymerase chain reaction. During recovery from hyperoxia, TRX-Tg mice exhibited an improved mean linear intercept length and increased number of secondary septa in lungs compared with the WT mice. Proinflammatory cytokines mRNA expression levels were reduced in the lungs of TRX-Tg mice compared with the WT mice during recovery from hyperoxia. These results suggest that in newborn mice TRX ameliorates hyperoxic lung injury during recovery likely through the suppression of proinflammatory cytokines.

Academic Significance and Societal Importance of the Research Achievements

TRXトランスジェニックマウスは新生仔期高濃度酸素暴露による高濃度酸素性肺傷害に対する防御効果を示した。炎症性マーカーであるIL-6 、MCP-1、CXCL2の肺内mRNA発現が有意に減少し、マクロファージの遊走を阻害した。本研究結果から、ヒト組み換えチオレドキシン蛋白は新生児慢性肺障害に対して有効である可能性があると考えられるが、臨床応用に向けては、新生児慢性肺障害マウスモデルに対するヒト組み換えチオレドキシン蛋白の有効性を検証する必要がある。

Research Products

• [Journal Article] Attenuation of Hyperoxic Lung Injury in Newborn Thioredoxin-1-Overexpressing Mice through the Suppression of Proinflammatory Cytokine mRNA Expression. (2020)
  • Author(s): Nagano N, Tanaka K, Ozawa J, Watanabe T, Miyake F, Matsumura S, Osada K, Matsuoka K, Tamura M, Namba F.
  • Journal Title: Biomedicines. Volume: 8 Issue: 3 Pages: 113-113
  • DOI: 10.3390/biomedicines8030066
  • Peer Reviewed / Open Access
• [Presentation] Human thioredoxin-1 enhances recovery from hyperoxic lung injury in newborn mice through the inhibition of proinflammatory cytokine gene expression (2018)
  • Author(s): Nobuhiko Nagano, Kousuke Tanaka, Kikumi Matsuoka, Yukio Arai2 Takaaki Watanabe2, Fuyu Miyake, Shun Matsumura, Masanori Tamura, Fumihiko Namba
  • Organizer: 米国小児科学会
  • Int'l Joint Research
• [Presentation] 新生児慢性肺疾患における細胞内抗酸化物質チオレドキシンの重要性 (2017)
  • Author(s): 長野伸彦、田中広輔、松岡菊美、田村正徳、難波文彦
  • Organizer: 新生児慢性肺疾患研究会