硫酸酯酶 1 介导 CCL5 通过血管平滑肌细胞减轻自发性高血压大鼠血管紧张素 II 诱导的高血压效应。
Sulfatase 1 mediates the attenuation of Ang II-induced hypertensive effects by CCL5 in vascular smooth muscle cells from spontaneously hypertensive rats.
机构信息
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
出版信息
Cytokine. 2018 Oct;110:1-8. doi: 10.1016/j.cyto.2017.12.027. Epub 2018 Apr 21.
Extracellular sulfatases, sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling and carcinogenesis. Chemokine CCL5 inhibits Ang II-induced hypertensive mediators via angiotensin II (Ang II) type 2 receptor (AT R) pathway in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). In this study, we investigated the effect of Sulfs on anti-hypertensive effects of CCL5 in SHR VSMCs. CCL5 attenuated Ang II-induced inhibition of sulfatase activity in SHR VSMCs. Inhibition of Ang II-induced 12-lipoxygenase (12-LO) and endothelin-1 (ET-1) expression by CCL5 was reduced in Sulf1 small interfering RNA (siRNA)-transfected SHR VSMCs. In addition, attenuation of Ang II-induced dimethylarginine dimethylaminohydrolase-1 (DDAH-1) inhibition by CCL5 was reduced in Sulf1 siRNA-transfected SHR VSMCs. Downregulation of Sulf2 did not affect inhibitory effects of CCL5 on Ang II-induced 12-LO and ET-1 expression and Ang II-induced inhibition of DDAH-1 expression in SHR VSMCs. Downregulation of Sulf1 abrogated the expression of CCL5-induced AT R messenger RNA (mRNA) and synergistic effect of CCL5 on Ang II-induced AT R expression in SHR VSMCs. These findings suggest that Sulf1 is a potential up-regulatory factor in anti-hypertensive actions of CCL5 via AT R pathway on Ang II-induced hypertensive effects in SHR VSMCs.
细胞外硫酸酯酶，硫酸酯酶 1（Sulf1）和硫酸酯酶 2（Sulf2），在细胞信号转导和致癌作用中发挥关键作用。趋化因子 CCL5 通过血管平滑肌细胞（VSMCs）中的血管紧张素 II 型 2 型受体（AT R）途径抑制血管紧张素 II（Ang II）诱导的高血压介质。在这项研究中，我们研究了 Sulfs 对 CCL5 在自发性高血压大鼠（SHR）VSMCs 中的抗高血压作用的影响。CCL5 减弱了 Ang II 诱导的 SHR VSMCs 中硫酸酯酶活性的抑制。在 Sulf1 小干扰 RNA（siRNA）转染的 SHR VSMCs 中，CCL5 抑制 Ang II 诱导的 12-脂氧合酶（12-LO）和内皮素-1（ET-1）表达减少。此外，在 Sulf1 siRNA 转染的 SHR VSMCs 中，CCL5 减弱 Ang II 诱导的二甲基精氨酸二甲氨基水解酶-1（DDAH-1）抑制作用减少。下调 Sulf2 不会影响 CCL5 对 Ang II 诱导的 12-LO 和 ET-1 表达以及 Ang II 诱导的 DDAH-1 表达的抑制作用在 SHR VSMCs 中。下调 Sulf1 消除了 CCL5 诱导的 AT R 信使 RNA（mRNA）表达和 CCL5 对 Ang II 诱导的 SHR VSMCs 中 AT R 表达的协同作用。这些发现表明，Sulf1 是 CCL5 通过 AT R 途径在 Ang II 诱导的 SHR VSMCs 高血压效应中发挥抗高血压作用的潜在上调因子。
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