Basal cells express functional TRPV4 channels in the mouse nasal epithelium.
Basal cells express functional TRPV4 channels in the mouse nasal epithelium.
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DOI：
10.1016/j.bbrep.2015.09.008
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发表时间：
2015-12
影响因子：
2.7
通讯作者：
Ugawa S
中科院分区：
文献类型：
--
作者：
Ueda T;Hoshikawa M;Shibata Y;Kumamoto N;Ugawa S
鼻上皮（嗅上皮和气道上皮）中的基底细胞是能够分裂、更新和分化为特化细胞的干细胞/祖细胞。这些干细胞可以感知其生物物理微环境，但这一过程的潜在机制尚不清楚。在这里，我们证明了瞬时受体电位香草样蛋白4 （TRPV4）通道的显著表达，这是一种Ca2+渗透性通道，已知作为低渗透和机械应力的传感器，存在于小鼠鼻上皮基底细胞中。TRPV4 mRNA在产前小鼠鼻上皮基底部表达，并在成年小鼠中持续表达。在野生型小鼠鼻上皮基底层也检测到TRPV4蛋白，但在TRPV4敲除（TRPV4- ko）小鼠中未检测到。trpv4阳性免疫反应在气道上皮中与基底细胞标志物角蛋白14 （K14）的免疫反应大部分重叠，在嗅觉上皮中与K14的免疫反应部分重叠。Ca2+成像分析显示，低渗透刺激和4α-phorbol 12,13 didecanoate （4α-PDD）都是TRPV4激动剂，可引起野生型小鼠鼻上皮上部培养的一组原代上皮细胞的胞浆Ca2+浓度升高。这种反应在TRPV4-KO小鼠上皮相似部位的细胞中几乎不明显。最后，正常情况下野生型与TRPV4-KO小鼠嗅上皮brdu标记增殖无显著差异。因此，TRPV4通道在整个鼻上皮的基底细胞中功能性表达，并可能作为基底干细胞发育和损伤诱导再生的传感器。TRPV4在鼻气道和嗅上皮的基底干细胞中表达。TRPV4在产前晚期出现在鼻上皮中。TRPV4激活引起胞浆内Ca2+浓度的增加。TRPV4可能参与祖细胞/干细胞的多种细胞功能。
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. TRPV4 is expressed in basal stem cells of the nasal airway and olfactory epithelium. TRPV4 expression appears in the nasal epithelium during the late prenatal stages. TRPV4 activation causes an increase in cytosolic Ca2+ concentration. TRPV4 may be involved in a variety of cellular functions in progenitor/stem cells.