Abstract
Vocal folds are a viscoelastic multilayered structure responsible for voice production. Vocal fold epithelial damage may weaken the protection of deeper layers of lamina propria and thyroarytenoid muscle and impair voice production. Systemic dehydration can adversely affect vocal function by creating suboptimal biomechanical conditions for vocal fold vibration. However, the molecular pathobiology of systemically dehydrated vocal folds is poorly understood. We used an in vivo rabbit model to investigate the complete gene expression profile of systemically dehydrated vocal folds. The RNA-Seq based transcriptome revealed 203 differentially expressed (DE) vocal fold genes due to systemic dehydration. Interestingly, function enrichment analysis showed downregulation of genes involved in cell adhesion, cell junction, inflammation, and upregulation of genes involved in cell proliferation. RT-qPCR validation was performed for a subset of DE genes and confirmed the downregulation of DSG1, CDH3, NECTIN1, SDC1, S100A9, SPINK5, ECM1, IL1A, and IL36A genes. In addition, the upregulation of the transcription factor NR4A3 gene involved in epithelial cell proliferation was validated. Taken together, these results suggest an alteration of the vocal fold epithelial barrier independent of inflammation, which could indicate a disruption and remodeling of the epithelial barrier integrity. This transcriptome provides a first global picture of the molecular changes in vocal fold tissue in response to systemic dehydration. The alterations observed at the transcriptional level help to understand the pathobiology of dehydration in voice function and highlight the benefits of hydration in voice therapy.
Highlights
Vocal folds are a viscoelastic multilayered structure located in the larynx composed of a stratified squamous epithelium and lamina propria overlying the thyroarytenoid muscle [1, 2]
Maintaining optimal systemic hydration may have a role in preserving the vocal fold tissue architecture and, Molecular pathobiology of vocal fold systemic dehydration its normal function. How these transcriptional changes reflect in the proteome of vocal folds is our focus of investigation. This is the first study to analyze the global gene expression profile of vocal folds using an in vivo model of systemic dehydration
Systemic dehydration altered the transcriptome of vocal folds by downregulating the gene expression of cell junction-related molecules, regulators of epithelial proliferation and differentiation, and keratins
Summary
Vocal folds are a viscoelastic multilayered structure located in the larynx composed of a stratified squamous epithelium and lamina propria overlying the thyroarytenoid muscle [1, 2]. The epithelium is the outermost layer of the vocal fold and, together with the mucus, is the first barrier to protect the vocal folds from insults [3, 4]. Molecular pathobiology of vocal fold systemic dehydration ncbi.nlm.nih.gov/geo/) under accession number GSE132765. All other relevant data are within the paper and its Supporting Information files
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