Dataset Information

Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Cofre-Leiva C

PROVIDER: S-EPMC10176878 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

Cofré-Leiva Camila C Camargo-Ayala Paola Andrea PA Vergara-Pérez Angela A Hernández-Olivos Romina R Sanhueza Sergio S Nova-Lamperti Estefanía E Zúñiga-Hernández Jessica J Rivera César C

BMC oral health 20230511 1

<h4>Background</h4>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.<h4>Methods</h4>In this case-crossover study, we assessed the salivary proteome of patients with RAS (n = 36) ...[more]

PMID: 37170213

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Project description:BackgroundThe 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.MethodsTo 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.ResultsThe 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.ConclusionThe 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.

Project description:Recurrent aphthous stomatitis (RAS) is the most common disease affecting oral mucosae. Etiology is unknown, but several factors have been implicated, all of which influence the composition of microbiota residing on oral mucosae, which in turn modulates immunity and thereby affects disease progression. Although no individual pathogens have been conclusively shown to be causative agents of RAS, imbalanced composition of the oral microbiota may play a key role. In this study, we sought to determine composition profiles of bacterial microbiota in the oral mucosa associated with RAS. Using high-throughput 16S rRNA gene sequencing, we characterized the most abundant bacterial populations residing on healthy and ulcerated mucosae in patients with RAS (recruited using highly stringent criteria) and no associated medical conditions; we also compared these to the bacterial microbiota of healthy controls (HCs). Phylum-level diversity comparisons revealed decreased Firmicutes and increased Proteobacteria in ulcerated sites, as compared with healthy sites in RAS patients, and no differences between RAS patients with healthy sites and HCs. Genus-level analysis demonstrated higher abundance of total Bacteroidales in RAS patients with healthy sites over HCs. Porphyromonadaceae comprising species associated with periodontal disease and Veillonellaceae predominated in ulcerated sites over HCs, while no quantitative differences of these families were observed between healthy sites in RAS patients and HCs. Streptococcaceae comprising species associated with oral health predominated in HCs over ulcerated sites but not in HCs over healthy sites in RAS patients. This study demonstrates that mucosal microbiome changes in patients with idiopathic RAS--namely, increased Bacteroidales species in mucosae of RAS patients not affected by active ulceration. While these changes suggest a microbial role in initiation of RAS, this study does not provide data on causality. Within this limitation, the study contributes to the understanding of the potential role of mucosal microbiome changes in oral mucosal disease.

Dataset Information

Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

Background

Methods

Results

Conclusion

Publications

Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

Similar Datasets

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