Low level expression of PDZ and LIM domain protein 2 (PDLIM2) human gingival fibroblasts is indicative of severe periodontal inflammation in Down syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18768
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Nihon University
• Principal Investigator: YAGUCHI Manabu 日本大学, 松戸歯学部, 専修医 (90732181)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Down症候群 / 歯周病 / NF-κB / ユビキチンリガーゼ / PDLIM2

Outline of Final Research Achievements

Individuals with Down syndrome (DS) have a high prevalence of severe periodontitis, which develops early and proceeds rapidly, in comparison with healthy controls (non DS). The abnormal host responses have been considered to result in severe periodontal disease in individuals with DS. However, the mechanisms of development and procedure of periodontal inflammation in DS are not fully understood. The nuclear PDZ and LIM domain protein 2 (PDLIM2) acts an ubiquitin E3 ligase that targets the p65 subunit of　nuclear factor-kappa B (NF-κB), thus terminating NF-κB-mediated inflammation. In this study, we compared the gene and protein expression levels of PDLIM2 in the gingival fibroblasts from individuals with DS (DGF) and non DS (NGF). The gene and protein expression levels of PDLIM2 in DGF were constitutively lower than those in NGF. These data indicate that low level expression of PDLIM2 in DGF may be associated with the severe periodontal disease in DS patients.

Free Research Field

歯学

Academic Significance and Societal Importance of the Research Achievements

疾患の病態解明のために，その疾患特有の遺伝子に欠損もしくは変異が生じている遺伝性疾患を利用する手法が用いられており，近年，Down症候群（DS）由来細胞を用いたAlzheimer病の病態解明が大きな成果をあげている。本研究では，健常者と比べDS由来歯肉線維芽細胞で炎症を負に制御するPDLIM2の発現が恒常的に低かった。つまり，DSは炎症抑制遺伝子の欠損ないし変異が生じていると言える。本研究に使用した臨床サンプルは小児DS由来のため，経過を追うことで将来的な歯周病発症の有無を確認し，DSにおける免疫応答性の個体差を明らかにできれば，健常者における歯周病の病態解明にも応用できるものと考えられる。