Elucidation of corneal epithelial wound healing effect and wound healing mechanism by PACAP

• Project/Area Number: 18K09462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Hoshi University
• Principal Investigator: SHIBATO JUNKO 星薬科大学, 先端生命科学研究所, 寄附講座等客員助教 (10611121)
• Co-Investigator(Kenkyū-buntansha): 中町 智哉 富山大学, 学術研究部理学系, 講師 (30433840) ; RAKWAL RANDEEP 筑波大学, 体育系, 教授 (70590850) ; 塩田 清二 星薬科大学, 先端生命科学研究所, 教授 (80102375)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: PACAP / 角膜上皮細胞 / 創傷治癒 / マイクロアレイ / pacap / 角膜 / 角膜外皮 / 角膜上皮

Outline of Final Research Achievements

To elucidate the effect of neuropeptide PACAP on corneal epithelial wound healing, the factors involved in wound healing were investigated in this study. Results of DNA microarray and pathway analyses of corneal epithelial cells showed greater variability of the ERK genes in the PACAP group and JNK genes in the PACAP + scratch group. Since the main effect of PACAP on wound healing was cell proliferation, we selected Nr4a1, which is important for wound healing. It has been reported that nuclear phosphorylation of NR4A1 leads to loss of transcriptional activity and promotes cell death by nuclear export. Therefore, PACAP may contribute to cell survival and wound healing by maintaining the nuclear-localized transcriptional activity of NR4A1.

Academic Significance and Societal Importance of the Research Achievements

本研究でPACAPによる角膜上皮創傷治癒作用にNR4A1が関与し、さらにPACAPのNR4A1の脱リン酸化作用が角膜上皮細胞の増殖や細胞死を制御している可能性が明らかになった。今後さらなるPACAPとNR4A1の相互作用が明らかになれば、視力喪失のリスクを低減させる有効な角膜治療法の開発に役立つと考える。NR4A1は細胞増殖だけでなく線維症、抗血栓作用、血管新生、腫瘍形成制御など様々な細胞活動を制御に関わる分子である。よって本研究の成果は様々な疾患治療につながる可能性があると思われる。

Research Products

• [Presentation] 神経ペプチドPACAPによる角膜上皮の新生・再生作用 (2020)
  • Author(s): 石川 満理奈、柴藤 淳子、中町 智哉、平林 敬浩、竹ノ谷 文子、塩田 清二
  • Organizer: 日本薬学会
• [Presentation] Relation between ADNP and PACAPon tissue distribution, protective effect and trophic effect in neural tissue. (2019)
  • Author(s): Tomoya Nakamachi
  • Organizer: ADNP Family Conference and Scientific Symposium
  • Int'l Joint Research
• [Presentation] Effect of PACAP on corneal epithelial repair (2019)
  • Author(s): Tomoya Nakamachi
  • Organizer: The Akira Arimura Memorial VIP/PACAP and Related Peptides Symposium: 30 years after PACAP Discovery
  • Int'l Joint Research
• [Presentation] 神経ペプチドPACAPによる角膜上皮の新生・再生作用 (2018)
  • Author(s): 石川満理奈, 柴藤淳子, 平林敬浩, 石野茉由子, 山下道生, 竹ノ谷文子, 塩田清二
  • Organizer: 日本薬学会