Matsumoto Kenjiro, Kato Shinichi
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University.
Nihon Yakurigaku Zasshi. 2019;154(3):92-96. doi: 10.1254/fpj.154.92.
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that responds to mechanical, thermal, and chemical stimuli in addition to various endogenous ligands, such as arachidonic acid metabolites. The present study aimed to elucidate the expression of TRPV4 in the gastrointestinal tract and the pathogenic roles of TRPV4 in dextran sulphate sodium (DSS)-induced colitis. TRPV4-immunoreactivity was detected in epithelial-like cells of the mouse tongue, esophagus, stomach, ileum, and colon; TRPV4 expression in the tongue was higher than other gastrointestinal tracts. TRPV4 colocalized with a type IV cell marker sonic hedgehog in circumvallate papillae. These findings suggest that TRPV4 contributes to sour taste sensing by regulating type III taste cell differentiation in mice. DSS-induced colitis was significantly attenuated in TRPV4-knockout (TRPV4KO) mice when compared to wild-type mice. DSS treatment upregulated TRPV4 expression in vascular endothelia of colonic mucosa and submucosa. DSS treatment increased vascular permeability, which was abolished in TRPV4KO mice. The activation of TRPV4 decreased VE-cadherin expression in mouse aortic endothelial cells exposed to TNF-α. These findings indicate that the upregulation of TRPV4 in vascular endothelial cells contributes to the progression of colonic inflammation via the activation of vascular permeability. Thus, TRPV4 is an attractive target for the treatment of inflammatory bowel diseases.
瞬时受体电位香草酸亚型4（TRPV4）是一种非选择性阳离子通道，除了能对多种内源性配体（如花生四烯酸代谢产物）作出反应外，还能对机械、热和化学刺激产生应答。本研究旨在阐明TRPV4在胃肠道中的表达情况以及TRPV4在硫酸葡聚糖钠（DSS）诱导的结肠炎中的致病作用。在小鼠的舌、食管、胃、回肠和结肠的上皮样细胞中检测到TRPV4免疫反应性；舌中TRPV4的表达高于其他胃肠道。在轮廓乳头中，TRPV4与IV型细胞标志物音猬因子共定位。这些发现表明，TRPV4通过调节小鼠III型味觉细胞的分化来促进酸味感知。与野生型小鼠相比，TRPV4基因敲除（TRPV4KO）小鼠中DSS诱导的结肠炎明显减轻。DSS处理上调了结肠黏膜和黏膜下层血管内皮细胞中TRPV4的表达。DSS处理增加了血管通透性，而这在TRPV4KO小鼠中被消除。在暴露于肿瘤坏死因子-α的小鼠主动脉内皮细胞中，TRPV4的激活降低了VE-钙黏蛋白的表达。这些发现表明，血管内皮细胞中TRPV4的上调通过激活血管通透性促进了结肠炎症的进展。因此，TRPV4是治疗炎症性肠病的一个有吸引力的靶点。
