A new strategy for salivary gland regeneration using genetic database and drug repurposing

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03852
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Sakai Takayoshi 大阪大学, 大学院歯学研究科, 教授 (90379082)
• Co-Investigator(Kenkyū-buntansha): 野原 幹司 大阪大学, 大学院歯学研究科, 准教授 (20346167) ; 福本 敏 九州大学, 歯学研究院, 教授 (30264253)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 唾液腺

Outline of Final Research Achievements

We found that the p63 gene is expressed during salivary gland regeneration and is regulated by FGF7. The transcription factor p63, a component of the p53 family, has important functions in the development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of ΔNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, ΔNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that ΔNp63 is essential for SG regeneration and may be a new target for regenerative treatment.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

唾液腺再生時にp63遺伝子が発現すること、p63アイソフォームであるΔNp63がFGF7によって制御されることを見出した。さらに、p38 MAPK リン酸化を介した FGF7 刺激によってΔNp63が調節され、唾液腺の形態形成に影響を与えることを明らかにした。すなわち、p38 MAPKのリン酸やFGF7 刺激が誘導するΔNp63を制御できる薬剤を見出せば、唾液腺の再生を誘導できるかもしれない。薬剤を用いた臓器再生を誘導できる候補薬剤を見出す突破口になればと考えて、研究を継続している。