Loss of TRPV4 impairs mucin secretion and salivary rheological properties in male mouse sublingual glands.

Transient receptor potential cation channel subfamily V member 4 (TRPV4) is implicated in salivary secretion; however, its role in mucin secretion in mouse sublingual glands (SLGs) remains unclear. This study used an ex vivo perfusion model to investigate the contribution of TRPV4 to mucin secretion and the rheological properties of saliva in wild-type (Trpv4⁺/⁺) and knockout (Trpv4⁻/⁻) male mice (8-12 weeks old) subjected to carbachol stimulation. Mucin content was assessed by N-acetylgalactosamine (GalNAc) fluorescent labeling, viscoelasticity by spinnbarkeit analysis, and MUC19 expression by immunohistochemistry, quantitative PCR, and western blot. Pharmacological TRPV4 inhibition with RN1734 was also performed in Trpv4⁺/⁺ SLGs. Salivary flow rate, pH, Ca²⁺, and total protein concentration were comparable between genotypes. GalNAc concentration and spinnbarkeit were significantly reduced in Trpv4⁻/⁻ SLG saliva, and RN1734 treatment in Trpv4⁺/⁺ SLGs reproduced these reductions. Muc19 mRNA expression and intracellular MUC19 distribution were unaffected, whereas MUC19 protein in secreted saliva was significantly lower in Trpv4⁻/⁻ mice. These findings indicate that TRPV4 contributes to mucin secretion in SLG acinar cells independently of fluid secretion and Muc19 transcriptional regulation, likely at the level of exocytosis.