Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

Abstract

The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal transduction.

Trpm7 Protein Contributes to Intercellular Junction Formation in Mouse Urothelium

“…In the urothelium, Trpm7 protein was predominantly expressed in the superficial layer as reported previously (Fig. 2D) (26). This layer is composed of "umbrella cells" with long narrow rectangular shapes (13,14).…”

Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization

“…In humans, TRPV1 mRNA was detected in the prostate, testis, penis, bladder, and extrinsic sensory neurons innervating these organs (42). In the urinary bladder, TRPV1 is expressed mostly in the detrusor smooth muscle, urothelium, interstitial cells within lamina propria (8,33,48), and on the blood vessels in the bladder wall (19). TRPV1 is also abundantly expressed in primary sensory neurons projecting to the pelvic viscera.…”

Impact of diabetes mellitus on bladder uroepithelial cells

“…3, B and C) may be involved in a chronic augmentation of UT membrane trafficking to accommodate increased urine volumes. In addition to changes in purinergic receptors, TRPV1 transcript has been reported in rodent (8,27,79) and human (50) UT, where it is has been proposed to act as a polymodal receptor and play a role in UT mechanosensation (5). Here we report significant elevation in TRPV1 gene expression in the UT of STZ-diabetic rats (Fig.…”