Preliminary Transcriptomic Effects of Lateralized RLN Denervation in Rat Vocal Fold.

Area of Science:

• Vocal fold physiology and molecular biology.
• Nerve injury and tissue regeneration.
• Transcriptomics and bioinformatics.

Background:

• Unilateral recurrent laryngeal nerve (RLN) injury is a common cause of vocal dysfunction.
• Understanding the molecular mechanisms underlying vocal fold response to denervation is crucial for developing targeted therapies.
• Previous studies have not fully elucidated the side-specific transcriptomic alterations in vocal fold compartments.

Purpose of the Study:

• To investigate whether unilateral RLN transection induces side-specific transcriptomic changes in rat vocal fold muscle and mucosa.
• To compare the molecular responses between the left and right vocal fold compartments after denervation, considering baseline laterality.

Main Methods:

• Adult rats underwent unilateral RLN transection.
• Vocal fold medial thyroarytenoid (MTA) muscle and mucosa were harvested 5 weeks post-injury for RNA sequencing.
• Differential gene expression analysis was performed to compare denervated tissues.
• Transcription factor (TF) activity was inferred, and baseline laterality was assessed to contextualize findings.

Main Results:

• Left RLN denervation resulted in distinct transcriptomic profiles in both vocal fold compartments.
• Mucosa showed reduced epithelial stability TFs and activated regenerative cues, indicating impaired differentiation.
• MTA displayed increased TFs related to stress signaling and mitochondrial compensation, with reduced epigenetic stability TFs.
• Lateralized activity in developmental regulators and pathway enrichment in skeletal development (MTA) and immune/matrix regulation (mucosa) were observed.

Conclusions:

• Recurrent laryngeal nerve injury induces significant, side-specific transcriptomic alterations in vocal fold muscle and mucosa.
• Left-sided denervation is associated with more pronounced atrophy and stress responses.
• These findings underscore the critical role of laterality in vocal fold adaptation following nerve injury.