Involvement of Integrated Stress (ISR) in Gingival Epithelial Barrier Function

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21084
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Osaka University
• Principal Investigator: Narukawa Yuki 大阪大学, 大学院歯学研究科, 特任研究員 (40910188)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 歯周病 / 糖尿病 / 歯肉上皮細胞 / 細胞間接着分子 / 酸化ストレス / 統合ストレス

Outline of Final Research Achievements

The decreased expression of intercellular adhesion molecules was observed in hyperglycemic gingival epithelial cells as a result of the increase in ROS. NAC, an antioxidant, significantly inhibited the decreased expression of intercellular adhesion molecules in hyperglycemic gingival epithelial cells. Furthermore, the expression of ATF4, a transcription factor as a family of the integrated stress response, was decreased or ERK1/2 phosphorylation was increased in gingival epithelial cells under hyperglycemia, and NAC had an inhibitory effect on ERK1/2 phosphorylation.
These results suggest that hyperglycemia induces a decrease in the expression of intercellular adhesion molecules by activating ERK1/2 in gingival epithelial cells and that oxidative stress and integrative stress responses are involved as the mechanism of these responses.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、糖尿病の病態である高血糖が歯周病を悪化させる一因を歯肉上皮細胞の細胞間接着分子に着目し、そのメカニズムを解析したものである。高血糖状態の歯肉上皮細胞において活性酸素の産生亢進やAFT4の発現低下を認め、酸化ストレスや統合ストレス応答と関連していることが示唆された。これらの研究成果は、糖尿病患者の歯周病悪化を予防する抗酸化剤などの新薬開発につながると考える。