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首页> 外文期刊>Cytokine >Sulfatase 2 mediates, partially, the expression of endothelin-1 and the additive effect of Ang II-induced endothelin-1 expression by CXCL8 in vascular smooth muscle cells from spontaneously hypertensive rats
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Sulfatase 2 mediates, partially, the expression of endothelin-1 and the additive effect of Ang II-induced endothelin-1 expression by CXCL8 in vascular smooth muscle cells from spontaneously hypertensive rats

机译:硫酸糖酶2介导,部分地,内皮素-1的表达和CXCL8在自发性高血压大鼠中CXCL8在血管平滑肌细胞中的血管平滑肌蛋白-1表达的表达。

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摘要

The extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), have an important role in cell signaling by modulating the 6-O-sulfation of heparan sulfate proteoglycans (HSPGs) on the cell surface. Gene expression and enzyme activity of Sulfs are elevated in hypertensive vascular smooth muscle cells (VSMCs) compared to those in normotensive VSMCs. CXC-chemokine ligand (CXCL) 8 has a pathogenic role in the development and progression of hypertension. In this study, we investigated the effect of Sulfs on the expression of CXCL8-induced endothelin (ET)-1, a hypertensive mediator, in VSMCs from spontaneously hypertensive rats (SHR). Expression of ET-1 and elevation of angiotensin (Ang) II-induced ET-1 expression by CXCL8 were reduced in Sulf2 small interfering RNA (siRNA)-transfected SHR VSMCs. But, downregulation of Sulfl did not affect the expression of CXCL8-induced ET-1 and additive effect of CXCL8 on Ang II-induced ET-1 expression in SHR VSMCs. CXCL8-induced ET-1 expression and the additive effect of CXCL8 on Ang II-induced ET-1 expression were dependent on the Ang II type 1 receptor (AT(1) R) pathway, not the Ang II type 2 receptor (AT(2) R) pathway. In addition, downregulation of Sulf2 reduced the expression of CXCL8-induced AT, R and abrogated the additive effect of CXCL8 on Ang II-induced AT(1) R expression in SHR VSMCs. Sulf2 mediated, partially, the expression of ET-1 and the additive expression of Ang II-induced ET-1 mRNA by CXCL8 via the AT(1) R pathway in SHR VSMCs. These findings suggest that Sulf2 is an up-regulatory factor in the additive action of CXCL8 via the AT(1) R pathway on Ang II-induced ET-1 expression in VSMCs under hypertension environment.
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