Bhargave Geeta, Woodworth Bradford A, Xiong Guoxiang, Wolfe Steven G, Antunes Marcelo B, Cohen Noam A
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
Am J Rhinol. 2008 Jan-Feb;22(1):7-12. doi: 10.2500/ajr.2008.22.3125.
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).
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.
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.
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.
瞬时受体电位（TRP）通道是一类新型的非电压门控膜阳离子通道，可被机械刺激和温度变化激活。最近，TRP香草酸受体4型（TRPV4）被认为参与检测输卵管上皮细胞的粘度变化并诱导纤毛活动的代偿反应，因此，它可能是调节呼吸道纤毛活动的分子触发因素。因此，本研究的目的是确定TRPV4在人鼻黏膜中的表达模式，并确定其在慢性鼻窦炎（CRS）中表达是否改变。
从CRS患者、伴有鼻息肉（NP）的CRS患者和健康对照者中获取鼻窦黏膜活检标本。分别通过逆转录聚合酶链反应（RT-PCR）和免疫印迹分析确认TRPV4 mRNA和蛋白表达。接下来使用定量RT-PCR测量TRPV4基因表达。对鼻窦黏膜外植体和呼吸道上皮气液界面培养物进行免疫荧光，以定位细胞表达。
所有样本中均表达TRPV4 mRNA和蛋白。非息肉样CRS患者的TRPV4基因表达有统计学显著增加（p < 0.05），但伴有NP的CRS患者无差异。双标免疫荧光显示TRPV4表达与纤毛细胞相互排斥。
尽管TRPV4是纤毛调节的理想分子触发因素，但该通道在纤毛细胞中缺乏表达排除了此功能。然而，CRS中该通道表达的改变以及黏膜分泌细胞中TRPV4的推测表达表明其在黏液稳态和CRS发病机制中具有潜在作用。
