Elucidation of the role of TRP channels and midkine in keratinocyte-neuron interactions.

Research Project

Project/Area Number	18K09476
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56070:Plastic and reconstructive surgery-related
Research Institution	Tokyo Medical and Dental University
Principal Investigator	MORI Hiroki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80345305)
Co-Investigator(Kenkyū-buntansha)	植村法子東京医科歯科大学, 医学部附属病院, 助教 (10568017) 田中顕太郎東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20569503)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	神経細胞 / 角化細胞 / 振盪刺激 / ミッドカイン / TRPV4 / タミバロテン / 物理刺激 / 神経再生 / TRPチャネル
Outline of Final Research Achievements	Among the skin-nerve interactions, physical stimulation was examined for Transient Receptor Potential Vanilloid 4(TRPV4) and midkine (MK), and MK-mediated nerve regeneration was also examined for Tamibarotene (AM 80). Physical stimulation using a shaker was used to examine the effect. The present study suggests that (1)TRPV4 expression in keratinocyte may be enhanced by shaking stimulation. (2) MK was highly expressed in both neuronal and kerationcyte cultures, suggesting its involvement. (3) MK was decreased by shaking stimulation. (3) MK was decreased by shaking. (4) Addition of Am80 (10μM) promoted neurite outgrowth and densification, but the effect on MK concentration was minor.
Academic Significance and Societal Importance of the Research Achievements	皮膚と神経の相互作用、および物理刺激による神経再生について過去の報告の追試、および新知見となりうる結果が得られた。①TRPV4については追試の域を出なかったが、②③MKの所見は新知見になりうる。また④Am80についてはMKへの影響は軽微にも関わらず神経突起の伸長が見られ、他の要素の可能性も示唆された。皮膚の知覚再建・再生にはいまだ不明な点が多いが、本研究はケラチノサイト・神経細胞の相互作用、さらに物理刺激を加えた点、またミッドカインおよびAm80の神経再生にケラチノサイト・神経細胞の相互作用と絡めた点で新規性があり、細胞の相互作用と物理刺激を多面的に捉えた研究となった。