Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8628709 | Cytokine | 2018 | 8 Pages |
Abstract
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 (AT2 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 AT2 R messenger RNA (mRNA) and synergistic effect of CCL5 on Ang II-induced AT2 R expression in SHR VSMCs. These findings suggest that Sulf1 is a potential up-regulatory factor in anti-hypertensive actions of CCL5 via AT2 R pathway on Ang II-induced hypertensive effects in SHR VSMCs.
Keywords
DDAH-1CCL12-LOCcl5VSMCCXCLET-1AMPKeNOS12-lipoxygenaseCC-chemokine ligandSulf2ANG II type 2 receptorADMADMEMFBSCXC-chemokine ligandAMP-activated protein kinasecDNAComplementary DNAHSPGsSmall interfering RNAsiRNAAngiotensin IIEDTAEthylenediaminetetraacetic acidendothelin-1standard error of the meansSpontaneously Hypertensive RatAng IIfetal bovine serumVascular smooth muscle cellendothelial nitric oxide synthaseSulf1SulfatasesShrHypertensionDulbecco’s modified eagle’s mediumSEMpolymerase chain reactionPCRheparan sulfate proteoglycansANG II type 1 receptor
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Authors
Hye Ju Cha, Hye Young Kim, Hee Sun Kim,