TRPA1-expressing lamina propria mesenchymal cells regulate colonic motility
TRPA1-expressing lamina propria mesenchymal cells regulate colonic motility
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DOI：
10.1172/jci.insight.122402
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发表时间：
2019-05-02
期刊：
影响因子：
8
通讯作者：
Dai, Yi
中科院分区：
文献类型：
--
作者：
Yang, Yanjing;Wang, Shenglan;Dai, Yi
排便的生理过程直接受结直肠运动的控制。瞬时受体电位锚蛋白1（TRPA 1）通道在小肠肠嗜铬细胞中表达，并通过5-羟色胺释放参与胃肠动力。然而，在结直肠，肠嗜铬细胞的定位在很大程度上不同于小肠。在这里，我们研究了下胃肠道TRPA 1在调节结直肠运动中的作用。我们发现，在结肠组织中，TRPA 1主要表达在固有层的间充质细胞中，这与小肠中的细胞明显不同。这些细胞共表达COX 1和微粒体前列腺素E合酶-1。TRPA 1激动剂的结肠内给药诱导结肠收缩，其被前列腺素E2（PGE 2）受体1拮抗剂抑制。TRPA 1激活诱导培养的人成纤维细胞的钙内流和PGE 2释放。在葡聚糖硫酸钠治疗的动物中，TRPA 1及其内源性激动剂在结肠固有层中显著增加，伴有异常的结直肠收缩。TRPA 1的药理学和遗传学抑制显著预防了异常结直肠收缩。总之，在下胃肠道中，间充质TRPA 1激活导致PGE 2释放，从而促进结直肠收缩，代表我们认为是一种新的生理和炎症性肠病相关的胃肠动力机制。
The physiological process of defecation is directly controlled by colorectal motility. The transient receptor potential ankyrin 1 (TRPA1) channel is expressed in small intestine enterochromaffin cells and is involved in gastrointestinal motility via serotonin release. In the colorectum, however, enterochromaffin cell localization is largely distinct from that in the small intestine. Here, we investigated the role of lower gastrointestinal tract TRPA1 in modulating colorectal motility. We found that in colonic tissue, TRPA1 is predominantly expressed in mesenchymal cells of the lamina propria, which are clearly distinct from those in the small intestine. These cells coexpressed COX1 and microsomal prostaglandin E synthase-1. Intracolonic administration of TRPA1 agonists induced colonic contraction, which was suppressed by a prostaglandin E2 (PGE2) receptor 1 antagonist. TRPA1 activation induced calcium influx and PGE2 release from cultured human fibroblastic cells. In dextran sulfate sodium-treated animals, both TRPA1 and its endogenous agonist were dramatically increased in the colonic lamina propria, accompanied by abnormal colorectal contractions. Abnormal colorectal contractions were significantly prevented by pharmacological and genetic inhibition of TRPA1. In conclusion, in the lower gastrointestinal tract, mesenchymal TRPA1 activation results in PGE2 release and consequently promotes colorectal contraction, representing what we believe is a novel physiological and inflammatory bowel disease-associated mechanism of gastrointestinal motility.