[The Protective Function of TRPV4 in Interstitial Cystitis/Bladder Pain Syndrome]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder disorder of unknown etiology, characterized by pelvic and/or bladder pain accompanied by lower urinary tract symptoms such as urinary frequency and urgency. Currently, sufficiently effective pharmacological treatments are lacking. The non-selective cation channel, transient receptor potential vanilloid 4 (TRPV4), which is expressed in the bladder, responds to mechanical stretch. Its contribution to immune responses in an environment-dependent manner, positions it as a promising potential therapeutic target. I investigated the effects of TRPV4 activation on inflammatory responses and painful bladder hypersensitivity in a lipopolysaccharide (LPS)-induced IC/BPS rat model. Co-instillation of the selective TRPV4 agonist GSK1016790A (GSK) with LPS into the rat bladder alleviated LPS-induced bladder inflammation and modulated macrophage polarization. Moreover, GSK mitigated the LPS-induced increase in bladder pain-related behaviors and voiding frequency. Cytokine analysis revealed the suppression of multiple pro-inflammatory chemokines. These findings suggest that TRPV4 regulates innate immune responses in the bladder, thereby contributing to inflammation resolution and tissue protection, and underscore its potential as a novel therapeutic strategy for IC/BPS. In this review, I integrate my research findings and previous advances in the field to summarize the functional roles of TRPV4 in the bladder.