The Mechanoreceptor TRPV4 is Localized in Adherence Junctions of the Human Bladder Urothelium: A Morphological Study

Abstract

Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.

Functional Role for Piezo1 in Stretch-evoked Ca2+ Influx and ATP Release in Urothelial Cell Cultures

“…This heightened sensitivity might be related to the fact that Piezo1 does not require any other proteins for its activation and could be directly activated by membrane stretch (32,33,42). In contrast, TRPV4 interacts with the actin cytoskeleton (47) to form a mechanosensory complex (48) and is activated by an endogenous ligand, epoxyeicosatrienoic acid, a metabolite of arachidonic acid, although TRPV4 expressed in Xenopus oocytes has been reported to be directly activated by membrane stretch (25).…”

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

“…Whereas TRPV4 is present in the majority (.80%) of lumbar DRG neurons, no TRPV4-like immunoreactivity was detected in bladder afferents. In human urothelium, TRPV4 was localized adjacent to the adherence junctions (Janssen et al, 2011). Interestingly, TRPV4 seems to be highly coexpressed with TRPV2 and TRPM7 in both mouse (Everaerts et al, 2010a) and human (Shabir et al, 2013) urothelial cells.…”

Urothelial Signaling

“…TRPV1 is present and active both in the urothelium and in the nerve fibers of several species including humans (69). TRPV4 was initially described in the urothelium of rodents and humans (146). Coexpression of the two receptors was observed in 20% of rat urothelial cells (167).…”