Elucidation of the role and mechanism of extracellular signal-regulated kinase in upper airway stenosis
| Project/Area Number |
19K18782
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
Kimura Akari 北里大学, 医学部, 助教 (40623137)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 気管狭窄 / 細胞外シグナル調節キナーゼ / マウス気管狭窄モデル / MEK阻害剤 / 気管狭窄予防 / ERK / 咽喉頭気管粘膜疾患 |
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| Outline of Research at the Start |
気管狭窄・瘢痕声帯は外科手術を施行しても難治性・再発性の疾 患であり治療に難渋することが多い。今回、気管・咽喉頭の創傷治癒過程におけるExtracellular signal-regulated kinase 細胞外シグナル調節キナーゼ(ERK) のメカニズムの解明を目的とし研究を行う。ERK は遺伝子発現の調整、分裂、代謝、生存、アポトーシス、分化に関与するとされる細胞内シグナルである。 気管損傷による瘢痕モデルを作成し、ノックアウトマウスと ERK 阻害剤を用いて ERK1/2 それぞれの働きや役割を評価し、難治性疾患に対する新たな治療法の開発を目指し臨床応用への可能性を探る。
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| 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
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| 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。
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Report
(5 results)
Research Products
(5 results)
