Transcriptomic Effects of Lateralized RLN Denervation in Rat Vocal Fold (MTA & Mucosa)

Gary Gartling, PhD; Masayoshi Yoshimatsu, MD, PhD; Renjie Bing, MD; Ryan C. Branski, PhD
Department of Otolaryngology—Head & Neck Surgery, NYU Grossman School of Medicine, New York, NY

Abstract:

Objectives: To test whether unilateral recurrent laryngeal nerve (RLN) transection elicits side‑specific transcriptomic responses in rat vocal‑fold compartments. We compared the medial thyroarytenoid (MTA) muscle and mucosa on the left versus right, accounting for baseline laterality.
Methods: Unilateral RLN transection was performed in five adult rats (Left RLN: 2-males, 1-female; Right RLN: 1-male, 1-female). Five weeks post-injury, the medial thyroarytenoid (MTA) muscle and vocal fold mucosa were harvested for RNA sequencing. Differential expression analysis compared left- versus right-denervated tissues, while accounting for baseline asymmetry identified in naïve controls (1-male; 1-female). Transcription factor (TF) activity was inferred using perturbation-based signatures, and baseline trends were used to classify changes as unique to denervation, opposite, or consistent, to baseline direction.
Results: Left RLN denervation elicited distinct transcriptional responses in both compartments. In mucosa, TFs governing epithelial stability were reduced while regenerative cues were activated, suggesting impaired differentiation and recruitment of progenitor-like programs. In MTA, left-sided injury increased TFs consistent with stress signaling and mitochondrial compensation. TFs involved in epigenetic stability were reduced. Lateralized activity was observed in developmental regulators putatively related to positional memory or differential stress adaptation. Complementing these TF-level changes, pathway analysis revealed enrichment of skeletal development processes in MTA and immune/matrix regulation in mucosa, indicating coordinated remodeling across muscle and epithelial compartments.
Conclusion: RLN injury produces side-specific muscle and mucosal changes, with left-sided denervation showing stronger atrophy and stress responses. These results emphasize the importance of laterality and coordinated tissue adaptation.