首页> 外文期刊>Life sciences >Cardiac fibroblasts have functional TRPV4 activated by 4alpha-phorbol 12,13-didecanoate.
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Cardiac fibroblasts have functional TRPV4 activated by 4alpha-phorbol 12,13-didecanoate.

机译:心脏成纤维细胞具有由4Alpha-Phorbol 12,13-DideCanoate活化的功能性Trpv4。

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AIMS: Vanilloid type transient receptor potential channel (TRPV) could be a potential environmental sensor to multiple stimuli in many types of cells. In this study, we provide the first evidence of functional vanilloid type 4 transient receptor potential channel (TRPV4) in rat cardiac fibroblasts (CFs). MAIN METHODS: Expression of TRPV4 in CFs was analyzed at mRNA and protein level. Function of TRPV4 in CFs was evaluated using a selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alphaPDD) while measuring intracellular Ca(2+) concentration ([Ca(2+)](i)) and membrane currents. KEY FINDINGS: Analysis of expression of mRNA transcripts of TRPV subfamily revealed that TRPV2 and TRPV4 were expressed in CFs. Significant immunoreactivity to TRPV4 protein was also detected in CFs. When 4alphaPDD was applied to CFs, [Ca(2+)](i) was elevated in a concentration-dependent manner. The elevation of [Ca(2+)](i) was abolished by the removal of external Ca(2+) and by ruthenium red (RuR). 4alphaPDD also activated non-selective cation currents (NSCCs), which were suppressed by RuR. Moreover, pretreatment of CFs with short interference RNA (siRNA) targeting TRPV4 significantly reduced both 4alphaPDD-induced elevation of [Ca(2+)](i) and NSCC. SIGNIFICANCE: These results provide strong evidence that endogenous TRPV4 functions as an important regulator of [Ca(2+)](i) in CFs.
机译:目的:香草型瞬态受体电位通道(TRPV)可以是许多类型细胞中多种刺激的潜在环境传感器。在这项研究中,我们提供了大鼠心脏成纤维细胞(CFS)中的功能性香草型4瞬态受体电位通道(TRPV4)的第一证据。主要方法:在mRNA和蛋白质水平分析CFS中TRPV4的表达。使用选择性TRPV4激动剂,4Alpha-Phorbol 12,13-DideCanoate(4Alphapdd)评估TRPV4在CFS中的功能,同时测量细胞内Ca(2+)浓度([Ca(2 +)](I))和膜电流。关键发现:TRPV亚家族MRNA转录物的表达分析表明TRPV2和TRPV4在CFS中表达。在CFS中也检测到对TRPV4蛋白的显着免疫反应性。当将4Alphapdd施加到CFS时,以浓度依赖性方式升高[Ca(2 +)](I)。通过去除外部Ca(2+)和钌红色(RUR)来消除[Ca(2 +)](I)的升高。 4Alphapdd还激活了非选择性阳离子电流(NSCC),其被Rur抑制。此外,具有短干扰RNA(siRNA)的CFS的预处理靶向TRPV4显着降低了[Ca(2 +)](I)和NSCC的升高。意义:这些结果提供了强有力的证据,即内源TRPV4作为CFS中[Ca(2 +)](I)的重要调节剂。

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