Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis

Abstract

The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of the human intestine. Previous studies have focused on the detection of TRPV mRNA levels in colon tissue of patients with inflammatory bowel disease (IBD) whereas little information exists regarding TRPV channel expression in the colonic epithelium. The aim of this study was to evaluate the expression levels of TRPV1, TRPV2, TRPV3 and TRPV4 in mucosa epithelial cells of colonic biopsies from patients with ulcerative colitis (UC) in comparison to colonic resections from non-IBD patients (control group). Immunohistochemistry, using specific antibodies and quantitative analyses of TRPV-immunostained epithelial cells, was performed in semi-serial sections of the samples. TRPV1 expression was significantly decreased whereas TRPV4 expression was significantly increased in the colonic epithelium of UC patients compared to patients in the control group (p < 0.05). No significant difference for TRPV2 and TRPV3 expression levels between UC and control specimens was detected (p > 0.05). There was no correlation between TRPV channel expression and the clinical features of the disease (p > 0.05). Further investigation is needed to clarify the role of TRPV channels in human bowel inflammatory response.

Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells

“…Intestinal cells are not expected to express a significant level of endogenous TRPV4 [40], and expression of WT TRPV4 already conferred a slight increase in invasive capacity, as already reported [31]. TRPV4 S823D, S824D, and T813D conferred a strong gain in invasion (Figure 2(c,e)).…”

Transient Receptor Potential Channels and Inflammatory Bowel Disease

“…Further study confirmed an increased expression of TRPV1 in inflamed tissue of active UC patients compared with noninflamed tissue, being associated with a relapse and continuous activity of disease (64,67). However, a downregulated expression of TRPV1 was also revealed in colonic biopsies from UC and CD patients (68,70,71), and Rizopoulos et al (70) found no significant correlation between TRPV1 expression and clinical features in UC patients. In experimental colitis models, TRPV1 expression was also found to be altered (68, 78-80, 83, 84, 86) ( Table 1).…”

“…The TRPV4 mRNA expression and TRPV4 immunoreactivity in colon were remarkably upregulated in IBD patients (70,72,76), in particular, serosal blood vessels with active inflammation were more densely innervated by TRPV4-positive fibers, which often co-localized with the infiltrating CD45 + cells (73,76). Meanwhile, TRPV4 activation could recruit macrophages and other immune cells through the induction of chemokines, such as IL-8 and MCP-1 (73).…”

Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

“…Most in vivo studies targeting TRPV1 in animal models of atherosclerosis use dietary capsaicin treatment to achieve improvement either in atherosclerotic plaque reduction or in the accompanying inflammation. As we indicated in the above section, oral capsaicin treatment cannot directly act on cardiac or intravascular TRPV1 receptors, therefore, a remote activation should be suggested, which likely involves TRPV1 receptors localized on the capsaicin-sensitive sensory nerve terminals [ 68 ] and/or the intestinal epithelial cells [ 69 ]. The ApoE −/− mouse is the most frequently used model to study atherosclerosis [ 70 ].…”