Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats.
10.12701/yujm.2017.34.1.43
- Author:
Hye Young KIM
1
;
Hye Ju CHA
;
Hee Sun KIM
Author Information
1. Department of Microbiology, Yeungnam University College of Medicine, Daegu, Korea. heesun@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Sulfatases;
Angiotensin II type 2 receptor;
Hypertension
- MeSH:
Angiotensin II*;
Angiotensins*;
Arachidonate 12-Lipoxygenase;
Blotting, Western;
Down-Regulation;
Endothelin-1;
Heparan Sulfate Proteoglycans;
Hypertension;
Muscle, Smooth, Vascular*;
Rats, Inbred SHR*;
Real-Time Polymerase Chain Reaction;
Receptor, Angiotensin, Type 2*;
RNA, Messenger;
Sulfatases
- From:Yeungnam University Journal of Medicine
2017;34(1):43-54
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). METHODS: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [³ H]-thymidine incorporation. RESULTS: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor (AT₂ R) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of AT₂ R inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of AT₂ R mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the AT₂ R pathway was mediated by Sulf1 in SHR VSMCs. CONCLUSION: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the AT₂ R pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.
