Transient receptor potential vanilloid type 4 channel expression in chronic rhinosinusitis.
BACKGROUND
Transient receptor potential (TRP) channels are a novel class of nonvoltage gated membrane cation channels that can be activated by mechanical stimulation and temperature change. Recently, TRP vanilloid type 4 (TRPV4) has been implicated in detecting viscosity changes in fallopian tube epithelial cells and inducing a compensatory response in ciliary activity and, as such, represents a possible molecular trigger for modulating respiratory ciliary activity. Thus, the goal of this study was to establish the expression pattern of TRPV4 in human sinonasal mucosa and determine whether expression is altered in chronic rhinosinusitis (CRS).


METHODS
Sinus mucosal biopsy specimens were obtained from patients with CRS, CRS with nasal polyps (NPs), and healthy controls. TRPV4 mRNA and protein expression were confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblot analysis, respectively. TRPV4 gene expression was measured next using quantitative RT-PCR. Immunofluorescence was performed on sinus mucosal explants and respiratory epithelial air-liquid interface cultures to localize cellular expression.


RESULTS
TRPV4 mRNA and protein were expressed in all samples. There was a statistically significant increase (p < 0.05) in TRPV4 gene expression in nonpolypoid CRS patients, but no difference in CRS with NP. Dual label immunofluorescence showed TRPV4 expression to be mutually exclusive of ciliated cells.


CONCLUSIONS
Although TRPV4 represents an ideal molecular trigger for ciliary modulation, absent expression of the channel in ciliated cells precludes this function. However, altered expression of the channel in CRS and presumed expression of TRPV4 in secretory cells of the mucosa indicate a potential role in mucus homeostasis and CRS pathogenesis.
Bhargave
Geeta
G
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
Woodworth
Bradford A
BA
Xiong
Guoxiang
G
Wolfe
Steven G
SG
Antunes
Marcelo B
MB
Cohen
Noam A
NA
D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D009997:Osmotic Pressure; D010256:Paranasal Sinuses / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012852:Sinusitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050916:TRPV Cation Channels / Q000096:biosynthesis / Q000235:genetics*
D015415:Biomarkers; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D012313:RNA