Transient Receptor Potential Vanilloid 4 blockade protects against experimental colitis in mice: a new strategy for inflammatory bowel diseases treatment?

Abstract

Recent reports suggested that the activation of Transient Receptor Potential Vanilloid 4 (TRPV4) receptors in the gastrointestinal tract has pro-inflammatory effects. In this study, we demonstrated for the first time that TRPV4 mRNA expression is up-regulated in patients with inflammatory bowel diseases (IBD). Furthermore, selective blockade of TRPV4 in the 2,4,6-trinitrobenzenesulfonic acid animal model alleviates colitis and pain associated with the intestinal inflammation. Our study indicates that TRPV4 may play a role in mechanisms of defense in intestinal inflammation and that TRPV4 may be an attractive target for future systemic or topic anti-inflammatory treatment in patients with IBD.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Since gut bacteria produce high amounts of PAR-2, TRPV4 (along with TRPV1 and TRPA1) may be an attractive pharmacological target to relieve visceral pain. This hypothesis has gained good experimental support by the demonstration of increased TRPV4 mRNA expression in patients with IBD and the efficacy of pharmacological TRPV4 antagonism in a mouse model (induced by TNBS) of colitis (Fichna et al, 2012). Of note, Src inhibitor-1 suppressed PAR-2-induced activation of TRPV4, indicating the importance of tyrosine phosphorylation (Poole et al, 2013).…”

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

“…In human tissue, TRPV4 has also been reported in intestinal epithelial, glial and infiltrated inflammatory cells [74]. In the human epithelial cell line Caco2, TRPV4 was found to be expressed at the basolateral side, but also weakly at the apical side [75].…”

Cathepsin S Causes Inflammatory Pain via Biased Agonism of PAR2 and TRPV4

“…Cat-S is also activated in inflammatory diseases including rheumatoid arthritis (4) and colitis (5). Given the established contributions of PAR 2 and TRPV4 to arthritis (63) and colitis (30,64,65), antagonists of Cat-S, PAR 2 , and TRPV4 may be valuable treatments for these and other inflammatory diseases.…”