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首页> 外文期刊>American Journal of Physiology >An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes.
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An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes.

机译：环境传感器TRPV4是人类滑膜细胞中细胞内Ca2 +的新型调节剂。

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摘要

The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation of intracellular Ca(2+) (Ca(2+)(i)) in several types of cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is a functional regulator of Ca(2+)(i) in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD) effectively elevated Ca(2+)(i) in the RA and CTR cells, which was abolished by the removal of external Ca(2+). Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with human TRPV4 (MH7A-V4), 4alphaPDD elevated the Ca(2+)(i) in a similar manner to those in the RA and CTR cells. Electrophysiological analysis also revealed that 4alphaPDD activated nonselective cationic currents in RA cells. Application of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca(2+)(i), but this does not occur when it was applied to MH7A cells. Treatment of RA but not MH7A cells with 4alphaPDD for 24 h reduced their production of IL-8. These results suggest that an environmental sensor, TRPV4, is a novel regulator of intracellular Ca(2+) in human synoviocytes.
机译：类香草素4型瞬态受体电位通道（TRPV4）的激活在调节细胞内Ca（2+）（Ca（2 +）（i））的几种类型的细胞（包括血管和感觉器官）中起强制性作用。在这项研究中，我们提供证据证明TRPV4是人类滑膜细胞中Ca（2 +）（i）的功能调节剂。尽管在风湿性关节炎（RA）和无（CTR）患者的滑膜细胞中均在mRNA和蛋白水平检测到TRPV4的显着表达，但人成纤维样滑膜细胞系MH7A的表达却较低。一致地，选择性TRPV4激动剂4α-佛波醇12,13-十二烷酸酯（4alphaPDD）有效地提高了RA和CTR细胞中的Ca（2 +）（i），这通过去除外部Ca（2+）而被取消。此外，高空被钌红（TRPV的阻滞剂）抑制了。在人类TRPV4（MH7A-V4）转染的MH7A细胞中，4alphaPDD以与RA和CTR细胞相似的方式升高Ca（2 +）（i）。电生理分析还显示，4alphaPDD激活了RA细胞中的非选择性阳离子电流。 227 mosM解决方案应用于RA和MH7A-V4细胞可提高其Ca（2 +）（i），但将其应用于MH7A细胞则不会发生。用4alphaPDD处理RA，但不处理MH7A细胞24小时，减少了IL-8的产生。这些结果表明环境传感器，TRPV4，是人类滑膜细胞内Ca（2+）的新型调节剂。

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