Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca, Chile.
Laboratorio de Histopatología Oral y Maxilofacial, Departamento de Estomatología, Facultad de Odontología, Universidad de Talca, Avenida Lircay S/N, Campus Norte Universidad de Talca, Talca, Oficina, N°4, Chile.
BMC Oral Health. 2023 May 11;23(1):279. doi: 10.1186/s12903-023-02955-7.
The death of oral keratinocytes is a crucial step in the emergence of recurrent aphthous stomatitis (RAS, also known as aphthae or aphthous ulcers). Since there are no experimental models available to research aphthous ulcers, little is understood about this process. We hypothesize that saliva can be a data bank of information that offers insights on epithelial damage.
In this case-crossover study, we assessed the salivary proteome of patients with RAS (n = 36) in the presence and absence of ulcers using discovery proteomics and bioinformatics. Additionally, we contrasted these patterns with those of healthy individuals (n = 31) who had no prior aphthous ulceration.
Salivary proteome showed that during the ulcerative phase, controlled cell death was downregulated. Due to its ability to distinguish between individuals with and without ulcers, the ATF6B protein raises the possibility that endoplasmic reticulum (ER) stress is responsible for the damage that leads to the death of oral keratinocytes. The high abundance of TRAP1 and ERN1 matches with this biological discovery. The type of death is immunogenic, according to the functional data found in a cell death database.
We identified a cellular process that can lead to the death of oral keratinocytes in the etiopathogenesis process of RAS. Future studies should be conducted to identify what is responsible for the increase in ER stress signaling that would lead to an anti-cell death response.
口腔角质细胞的死亡是复发性阿弗他口炎(RAS,也称为口疮或阿弗他溃疡)出现的关键步骤。由于目前尚无研究阿弗他溃疡的实验模型,因此对这一过程知之甚少。我们假设唾液可以作为信息数据库,提供有关上皮损伤的见解。
在这项病例交叉研究中,我们使用发现蛋白质组学和生物信息学评估了有(n=36)和无(n=36)口腔溃疡的 RAS 患者的唾液蛋白质组。此外,我们将这些模式与无先前阿弗他溃疡的健康个体(n=31)进行了对比。
唾液蛋白质组显示,在溃疡阶段,受控细胞死亡被下调。由于 ATF6B 蛋白能够区分有和无溃疡的个体,因此内质网(ER)应激可能是导致口腔角质细胞死亡的原因。TRAP1 和 ERN1 的高丰度与这一生物学发现相符。根据细胞死亡数据库中的功能数据,死亡类型具有免疫原性。
我们确定了 RAS 发病机制中可能导致口腔角质细胞死亡的细胞过程。未来的研究应旨在确定是什么导致 ER 应激信号的增加,从而导致抗细胞死亡反应。