Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP.
Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP.
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通过细胞外 ATP 在角质形成细胞和感觉神经元之间机械刺激诱发信号转导。
DOI：
10.1016/j.bbrc.2021.10.046
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发表时间：
2021
影响因子：
3.1
通讯作者：
Oka K.
中科院分区：
文献类型：
--
作者：
Shindo Y;Fujita K;Tanaka M;Fujio H;Hotta K;Oka K.
皮肤暴露于各种外部刺激。角质形成细胞是表皮中的主要细胞类型，与外周感觉神经元相互作用并调节神经元的活动。最近的研究表明，角质形成细胞在伤害感受中起着至关重要的作用，ATP是角质形成细胞向感觉神经元传递信号的主要介质之一。然而，尚未对ATP介导的从角质形成细胞到感觉背根神经节（DRG）神经元的信息流进行细胞水平的定量分析。在这项研究中，我们进行了细胞表面ATP和细胞内Ca 2+信号的同时成像使用iATPSnFR，定位于细胞膜外的遗传编码的ATP探针，和Ca 2+探针，呋喃红。用玻璃针机械刺激角质形成细胞后，在刺激区域周围观察到Ca 2+和ATP释放的增加，并且这些现象呈正相关。在培养的DRG神经元和角质形成细胞相邻的刺激角质形成细胞，增加细胞内Ca 2+浓度和细胞表面ATP水平的一侧更接近刺激的细胞进行检测。背根神经节神经元的Ca ~（2+）反应与输入ATP信号的比值明显大于角质形成细胞。我们发现DRG神经元比角质形成细胞对ATP更敏感，因此，当与角质形成细胞共培养时，只有DRG神经元对1 μM或更低浓度的ATP有反应。此外，由角质形成细胞的适度机械刺激引起的信号主要传递到DRG神经元。这些发现将是重要的，在进一步确定的详细机制的伤害性刺激在表皮。
The skin is exposed to various external stimuli. Keratinocytes, which are the main cell type in the epidermis, interact with peripheral sensory neurons and modulate neuronal activity. Recent studies have revealed that keratinocytes play crucial roles in nociception, and that ATP is one of the main mediators of signal transduction from keratinocytes to sensory neurons. However, no quantitative cellular level analyses of ATP-mediated information flow from keratinocytes to sensory dorsal root ganglion (DRG) neurons have been conducted. In this study, we performed simultaneous imaging of cell surface ATP and intracellular Ca2+signals using both iATPSnFR, a genetically encoded ATP probe localized to the outside of the cell membrane, and the Ca2+probe, Fura-red. Upon mechanical stimulation of the keratinocyte with a glass needle, an increase in Ca2+and ATP release were observed around the stimulated area, and these phenomena were positively correlated. In cultured DRG neurons and keratinocytes neighboring the stimulated keratinocyte, increased intracellular Ca2+concentration and levels of cell surface ATP on the side closer to the stimulated cell were detected. The ratio of Ca2+response to input ATP signal was significantly larger in DRG neurons than in keratinocytes. We found that DRG neurons were more sensitive to ATP than keratinocytes, and therefore, only DRG neurons responded to ATP at 1 μM or lower concentrations when in co-culture with keratinocytes. Moreover, signals caused by moderate mechanical stimulation of keratinocytes were transmitted predominantly to DRG neurons. These findings would be important in the further determination of the detailed mechanism of nociception in the epidermis.
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