Elucidation of pathophysiology and treatment of novel allergic rhinitis by analysis of neuropeptide (Galanin)

Research Project

Project/Area Number	17K11364
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Otorhinolaryngology
Research Institution	Kyorin University
Principal Investigator	Yokoi Hidenori 杏林大学, 医学部, 准教授 (80317487)
Co-Investigator(Kenkyū-buntansha)	川田往嗣杏林大学, 医学部, 助教 (80782846)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	アレルギー性鼻炎モデルマウス / 神経ペプチド / Galanin (GAL) / GAL receptor 2 (GALR2) / GALR2 antagonist / Galanin / Galanin receptor 2 / allergic rhinitis / mouse model / Galanin receptor 2 拮抗剤 / 鼻かき回数 / くしゃみ回数 / 増悪因子 / アレルギー性鼻炎 / アレルギー炎症
Outline of Final Research Achievements	The changes in the total protein levels of GAL and GALR2 did not change statistically with the increase of allergic inflammation. It was suggested that these molecules are constitutively expressed from control to inflammation of severe allergic rhinitis. GALR2 antagonists significantly suppressed the frequency of nasal rubbing and sneezing in severe allergic rhinitis. Localization of GALR2 was shown in nasal mucociliary epithelial cells and nasal gland cells. GALR2 were localized to ciliated epithelial and submucosal gland cells in all analyzed mice. As a result, galanin signal did not change with the progress of sensitization. It was suggested that galanin may not be the trigger of AR, but may be one of the exacerbating factors. Therefore, it was suggested that GAL and GALR2 are involved in AR inflammation, and its inhibition may be a new therapeutic method for AR.
Academic Significance and Societal Importance of the Research Achievements	アレルギー性鼻炎モデルマウスを用いて, 神経ペプチドGAL/GALR2の関与を解析した結果, GALR2 antagonistが重症アレルギー性鼻炎における鼻かきやくしゃみ回数を抑制したことを初めて解析した. アレルギー性鼻炎の症状発現の際に神経ペプチドGAL/GALR2が関与していることを意味しており, 新たなる病態の解明が得られた. この結果より, 将来的にアレルギー性鼻炎の創薬につながる可能性を秘めていると考えられる.