Elucidation of the role and mechanism of extracellular signal-regulated kinase in upper airway stenosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18782
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kitasato University
• Principal Investigator: Kimura Akari 北里大学, 医学部, 助教 (40623137)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 気管狭窄 / 細胞外シグナル調節キナーゼ

Outline of Final Research Achievements

Tracheal stenosis is a refractory and recurrent disease induced by excessive cell proliferation within the restricted tracheal space. We investigated the role of extracellular signal-regulated kinase (ERK), which mediates a broad range of intracellular signal transduction processes in tracheal stenosis and the therapeutic effect of the MEK inhibitor which is the upstream kinase of ERK. We histologically analyzed cauterized tracheas to evaluate stenosis using a tracheal stenosis mouse model.
The cauterized trachea increased the rate of stenosis compared with the control trachea. The phosphorylation rate of ERK was significantly increased at 5 min after the cauterization. The daily treatment group had suppressed stenosis compared with the non-inhibitor treatment group.
P-ERK activation after cauterization could play an important role in the tracheal wound healing process. Consecutive inhibition of ERK phosphorylation is a potentially useful therapeutic strategy for tracheal stenosis

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

気管瘢痕狭窄マウスモデルを作成した。ERK上流のMEK阻害剤を投与することによって気管狭窄・瘢痕予防効果の検討を行うことができた。
ERK1/2は気管狭窄に対する新規治療法の標的となる可能性がある。今後はERK1/2それぞれのノックアウトモデルを用いた研究も可能となると期待される。