Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity?
Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity?
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DOI：
10.1007/s00441-018-2926-7
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发表时间：
2019-03-01
影响因子：
3.6
通讯作者：
Schemann, Michael
中科院分区：
文献类型：
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作者：
Mazzuoli-Weber, Gemma;Kugler, Eva Maria;Schemann, Michael
压电通道在许多生理过程中起着重要的作用。它们在肠道神经系统中的存在和功能作用尚不清楚。我们假设它们在肠神经细胞的机械转导中发挥作用。我们的目标是利用免疫组织化学技术对Piezo1和Piezo2在整个胃肠道的肠神经元中的存在进行量化，并利用神经成像技术和药理学研究分析它们的功能(S)。为了进行系统和比较的研究，我们在豚鼠、小鼠和人的胃肠道组织中进行了实验。PIEZO1(20-70%)在所研究的所有物种的肌间神经丛和粘膜下神经丛的肠神经元体和神经纤维中都有表达。一般来说，Piezo1在胃以外的粘膜下神经丛(50-80%)比肌间神经丛(15%-35%)表达更多，在肌间神经丛高达60%的细胞体中表达Piezo1。肌间Piezo1神经元主要(60-100%)但不完全表达一氧化氮合酶，少数表达胆碱乙酰转移酶。在粘膜下神经丛中，Piezo1神经元共表达血管活性肠肽(40-90%)。相反，Piezo2在肠神经元体细胞中的表达非常罕见，在少数神经突起中也存在。在功能实验中，38-76%的机械敏感神经元表达Piezo1通道。统计分析表明，机械敏感神经元与Piezo1阳性神经元呈正相关。然而，使用Piezo通道激活剂和抑制剂的药理实验并没有显示机械转导的变化。可以排除Piezo1在肠神经元力学敏感性中的主要作用。
Piezo channels play fundamental roles in many physiological processes. Their presence and functional role in the enteric nervous system is still not known. We hypothesize that they play a role in mechanotransduction in enteric neurons. Our aims are to quantify the presence of both Piezo1 and 2 in enteric neurons throughout the gastrointestinal tract using immunohistochemistry and analyze their function(s) using neuroimaging techniques and pharmacological investigations. In order to perform a systematic and comparative study, we performed our experiments in gastrointestinal tissue from guinea pigs, mice and humans. Piezo1 (20-70%) is expressed by both enteric neuronal cell bodies and fibers in the myenteric and submucosal plexi of all the species investigated. Generally, Piezo1 expressing somata are more numerous in the submucosal plexus (50-80%) than in the myenteric plexus (15-35%) apart from the stomach where Piezo1 is expressed in up to 60% of cell bodies. Myenteric Piezo1 neurons mainly (60-100%) but not exclusively, also express nitric oxide synthase, a minority express choline acetyltransferase. In the submucosal plexus, Piezo1 neurons co-express vasoactive intestinal peptide (40-90%). Conversely, expression of Piezo2 is extremely rare in the somata of enteric neurons and is present in few neurites. In functional experiments, 38-76% of the mechanosensitive neurons expressed Piezo1 channels. Statistical analysis showed a positive significant correlation between mechanosensitive and Piezo1 positive neurons. However, pharmacological experiments using an activator and an inhibitor of Piezo channels did not demonstrate changes in mechanotransduction. A major role of Piezo1 in the mechanosensitivity of enteric neurons can be excluded.