Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
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。
