Basal cells express functional TRPV4 channels in the mouse nasal epithelium

Abstract

Basal cells in the nasal epithelium (olfactory and airway epithelia) are stem/progenitor cells that are capable of dividing, renewing and differentiating into specialized cells. These stem cells can sense their biophysical microenvironment, but the underlying mechanism of this process remains unknown. Here, we demonstrate the prominent expression of the transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca2+-permeable channel that is known to act as a sensor for hypo-osmotic and mechanical stresses, in the basal cells of the mouse nasal epithelium. TRPV4 mRNA was expressed in the basal portions of the prenatal mouse nasal epithelium, and this expression continued into adult mice. The TRPV4 protein was also detected in the basal layers of the nasal epithelium in wild-type but not in TRPV4-knockout (TRPV4-KO) mice. The TRPV4-positive immunoreactions largely overlapped with those of keratin 14 (K14), a marker of basal cells, in the airway epithelium, and they partially overlapped with those of K14 in the olfactory epithelium. Ca2+ imaging analysis revealed that hypo-osmotic stimulation and 4α-phorbol 12,13 didecanoate (4α-PDD), both of which are TRPV4 agonists, caused an increase in the cytosolic Ca2+ concentration in a subset of primary epithelial cells cultured from the upper parts of the nasal epithelium of the wild-type mice. This response was barely noticeable in cells from similar parts of the epithelium in TRPV4-KO mice. Finally, there was no significant difference in BrdU-labeled proliferation between the olfactory epithelia of wild-type and TRPV4-KO mice under normal conditions. Thus, TRPV4 channels are functionally expressed in basal cells throughout the nasal epithelium and may act as sensors for the development and injury-induced regeneration of basal stem cells.

Transient receptor potential vanilloid 4 mediates sour taste sensing via type III taste cell differentiation

“…Sonic hedgehog-positive cells are precursors for all taste cell types within taste buds 21 . It has been previously reported that TRPV4 is expressed in keratin 14-positive epidermal keratinocytes and in the olfactory and airway epithelia 22,23 . In this study, we also observed TRPV4 immunoreactivity in keratin 14-positive basal epithelial cells.…”

Polymodal Sensory Transduction in Mouse Corneal Epithelial Cells

“…TRPV4 has been identified as a key regulator of mechanically evoked cellular volume regulation, barrier permeability and immune interactions in lung, bladder, esophagus, skin, gut, kidney, choroid plexus, retinal pigment, and ciliary body epithelia. [17][18][19][20][21][22][23] TRPV4-mediated calcium influx has been linked to cytoskeletal reorganization, cell adhesion, formation of focal adhesions, and adenosine triphosphate (ATP)-dependent modulation of afferent excitation in epithelia, 5,19,24,25 yet mechanisms of TRPV4 gating are both celltype and context-specific, [26][27][28][29] and the properties of TRPV4 activation in native CECs have not been conclusively established. In this study, we employed imaging, electrophysiological, and molecular approaches to characterize calcium regulation and ATP release in CECs exposed to TRPV4 agonists, strain, volume, and temperature increases.…”