ABSTRACT
The swallowing reflex is an essential physiological reflex that allows food or liquid to pass into the esophagus from the oral cavity. Delayed triggering of this reflex is a significant health problem in patients with oropharyngeal dysphagia for which no pharmacological treatments exist. Transient receptor potential channels have recently been discovered as potential targets to facilitate triggering of the swallowing reflex. However, the ability of transient receptor potential vanilloid 4 (TRPV4) to trigger the swallowing reflex has not been studied. Here, we demonstrate the involvement of TRPV4 in triggering the swallowing reflex in rats. TRPV4 immunoreactive nerve fibers were observed in the superior laryngeal nerve (SLN)-innervated swallowing-related regions. Retrograde tracing with fluorogold revealed localization of TRPV4 on approximately 25% of SLN-afferent neurons in the nodose-petrosal-jugular ganglionic complex. Among them, approximately 49% were large, 35% medium, and 15% small-sized SLN-afferent neurons. Topical application of a TRPV4 agonist (GSK1016790A) to the SLN-innervated regions dose-dependently facilitated triggering of the swallowing reflex, with the highest number of reflexes triggered at a concentration of 250 µM. The number of agonist-induced swallowing reflexes was significantly reduced by prior topical application of a TRPV4 antagonist. These findings indicate that TRPV4 is expressed on sensory nerves innervating the swallowing-related regions, and that its activation by an agonist can facilitate swallowing. TRPV4 is a potential pharmacological target for the management of oropharyngeal dysphagia.
ABSTRACT
Cornified envelope formation is crucial for the final differentiation of keratinized epithelium. However, the mechanisms of cornified envelope formation in the oral epithelium remain unclear. The aim of this study was to clarify the differences in the distribution and expression of cornified envelope related proteins and genes between keratinized and non-keratinized oral epithelia. We immunohistochemically investigated the distribution patterns of transglutaminase 1 (TG1), transglutaminase 3 (TG3), and their substrate proteins involucrin (IVL), loricrin (LOR), and small proline rich proteins (SPRs), in 19 keratinized and 14 non-keratinized oral epithelium samples. TG1 and TG3 mRNA levels were investigated in both types of epithelium by real time reverse transcription polymerase chain reaction (RT-PCR) using paraffin-embedded specimens. Data were analyzed to identify factors involved in cornified envelope formation. We demonstrate that 11 localization patterns show statistically significant differences between keratinized and non-keratinized oral epithelia. These factors clearly drove the separation of the two groups during cluster analysis. TG1 mRNA levels in keratinized oral epithelium were significantly higher than those in non-keratinized oral epithelium. In conclusion, the characteristic distribution of transglutaminases and their substrates and the mRNA levels of TG1 can regulate cornified envelope formation in keratinized oral epithelium, together with the contribution of TG3 first reported in this paper.
