Laboratorio de Histopatología Oral y Maxilofacial, Unidad de Medicina Oral y Patología Oral, Departamento de Estomatología, Facultad de Odontología, Universidad de Talca, Avenida Lircay S/N, Campus Norte Universidad de Talca, Edificio de Ciencias Biomédicas, Oficina N°4, Talca, 3460000, Región del Maule, Chile.
BMC Oral Health. 2024 Sep 29;24(1):1154. doi: 10.1186/s12903-024-04917-z.
The exact cause of recurrent aphthous stomatitis is still unknown, making it a challenge to develop effective treatments. This study employs computational biology to investigate the molecular basis of recurrent aphthous stomatitis, aiming to identify the nature of the stimuli triggering these ulcers and the type of cell death involved.
To understand the molecular underpinnings of recurrent aphthous stomatitis, we used the Génie tool for gene identification, targeting those associated with cell death in recurrent aphthous stomatitis. The ToppGene Suite was employed for functional enrichment analysis. We also used Reactome and InteractiVenn for protein integration and prioritization against a PANoptosis gene list, enabling the construction of a protein-protein interaction network to pinpoint key proteins in recurrent aphthous stomatitis pathogenesis.
The study's computational approach identified 1,375 protein-coding genes linked to recurrent aphthous stomatitis. Critical among these were proteins responsive to bacterial stimuli, especially high mobility group protein B1 (HMGB1), toll-like receptor 2 (TLR2), and toll-like receptor 4 (TLR4). The enrichment analysis suggested an external biotic factor, likely bacterial, as a triggering agent in recurrent aphthous stomatitis. The protein interaction network highlighted the roles of tumor necrosis factor (TNF), NF-kappa-B essential modulator (IKBKG), and tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), indicating an immunogenic cell death mechanism, potentially PANoptosis, in recurrent aphthous stomatitis.
The findings propose that bacterial stimuli could trigger recurrent aphthous stomatitis through a PANoptosis-related cell death pathway. This new understanding of recurrent aphthous stomatitis pathogenesis underscores the significance of oral microbiota in the condition. Future experimental validation and therapeutic strategy development based on these findings are necessary.
复发性阿弗他口炎的确切病因仍不清楚，因此开发有效的治疗方法具有挑战性。本研究采用计算生物学方法研究复发性阿弗他口炎的分子基础，旨在确定触发这些溃疡的刺激物的性质和涉及的细胞死亡类型。
为了了解复发性阿弗他口炎的分子基础，我们使用基因识别工具 Génie 针对与复发性阿弗他口炎细胞死亡相关的基因。使用 ToppGene Suite 进行功能富集分析。我们还使用 Reactome 和 InteractiVenn 进行蛋白质整合，并针对 PANoptosis 基因列表进行优先级排序，构建蛋白质-蛋白质相互作用网络，以确定复发性阿弗他口炎发病机制中的关键蛋白。
该研究的计算方法确定了 1375 个与复发性阿弗他口炎相关的蛋白编码基因。其中关键的是对细菌刺激有反应的蛋白质，特别是高迁移率族蛋白 B1（HMGB1）、Toll 样受体 2（TLR2）和 Toll 样受体 4（TLR4）。富集分析表明，外部生物因素（可能是细菌）是复发性阿弗他口炎的触发因素。蛋白质相互作用网络突出了肿瘤坏死因子（TNF）、NF-kappa-B 必需调节剂（IKBKG）和肿瘤坏死因子受体超家族成员 1A（TNFRSF1A）的作用，表明复发性阿弗他口炎存在免疫原性细胞死亡机制，可能是 PANoptosis。
研究结果表明，细菌刺激可能通过与 PANoptosis 相关的细胞死亡途径触发复发性阿弗他口炎。对复发性阿弗他口炎发病机制的这一新认识强调了口腔微生物群在该疾病中的重要性。未来有必要基于这些发现进行实验验证和治疗策略开发。
