To identify novel therapy drug of Drug induced gingival overgrowth targeting NR4A1 by drug screening

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Shinji Matsuda 広島大学, 病院(歯), 病院助教 (30611321)
• Co-Investigator(Kenkyū-buntansha): 加治屋 幹人 広島大学, 医系科学研究科(歯), 助教 (00633041) ; 藤田 剛 広島大学, 医系科学研究科(歯), 准教授 (80379883)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 薬物性歯肉増殖症 / NR4A1 / ブチリデンフタリド

Outline of Final Research Achievements

Drug-induced giginval overgrowth (DIGO) is a side effect of CyclosporineA, Phenytoin and calcium channel blockers. The managemennt of DIGO is changing the drug and gingivectomy. However, for systemic condition and the role of drugs, there are limitation to use the current management for those patients. Therefore, the novel therapy is needed. The goal of the present stduy is to develop new therapy for DIGO. We previously identified a nuclear receptor (NR4A1) is associated with DIGO. NR4A1 function to improve firbrosis, but the three drugs disfunction of NR4A1. We hypothesized drugs which activate NR4A1 function will improve DIGO. The aim of the present study is to identify the chemical compound to activate NR4A1 and improve DIGO. We firstly used butylydenphtalide(BP) which increase the level of NR4A1. BP increased NR4A1 mRNA and protein levels in gigival fibroblasts and improved gingival overgrowth.

Free Research Field

歯周治療

Academic Significance and Societal Importance of the Research Achievements

これまでに、薬物性歯肉増殖症の決定的なメカニズム解明には至っていなかった。本研究では、歯肉増殖に関与する一つの分子を同定し、さらに治療法開発に応用できる可能性を追求できたことは大きな意義がある。今後さらなる研究が進めば、薬剤の変更や、歯肉切除術を必要としない、治療法の開発に繋がる可能性がある。
以上の点で、本研究の成果は意義があり、発展性がある重要な課題に取り組んだと考える。