Mechanism of promoting wound healing by the coordinated action of growth factors and neurotrophic factors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Sakai Hiroki 山口大学, 大学院医学系研究科, 助教 (40464367)
• Co-Investigator(Kenkyū-buntansha): 乾 誠 山口大学, その他部局等, 名誉教授 (70223237)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 創傷治癒 / 表皮細胞 / 成長因子 / 神経栄養因子 / アンギオテンシンII / アンギオテンシン変換酵素 / ペプチド

Outline of Final Research Achievements

Pain as an alert of wound is sensed by sensory nerves which might in turn play a role in the process of wound healing, although the mechanisms are largely unknown. Trophic effects of sensory nerves and growth factors play important roles in epithelial wound healing. Here we show that insulin-like growth factor (IGF-1) or a tetrapeptide (SSSR) derived from its C domain promotes keratinocyte migration independently of the IGF-1 receptor. Instead, this effect is mediated by angiotensin II generated by ACE in a manner dependent on activation of the NK1 receptor by the sensory neurotransmitter substance P or by its COOH-terminal tetrapeptide FGLM-NH2. Upon activation of NK1 receptor, SSSR induced shedding of ACE from keratinocytes, enhancing the ACE activity. Our results provide new insights into the interaction of sensory nerves and growth factors in wound healing as well as a foundation for a potential new peptide-based treatment of skin wounds.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかにした成長因子IGF-1と神経栄養因子サブスタンスPの協調作用による創傷治癒の促進メカニズムは、これまでに知られていない新たな病態生理学的機序の解明である。IGF-1がNK1受容体活性化の下でACE活性化を介して作用を発揮するというIGF受容体非依存性のメカニズムは、生物学的にも重要な意味を持つ可能性がある。また、SSSR標的分子を同定するツールとして合成に成功したNBD-SSSRは、SSSRの創傷治癒促進メカニズムの全容解明を可能にするだけでなく、そのメカニズムを基盤とした新たな創傷治癒促進薬の開発にも繋がる可能性がある。