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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
- Source :
- Cytokine. 114:98-105
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 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 Sulf1 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 (AT1 R) pathway, not the Ang II type 2 receptor (AT2 R) pathway. In addition, downregulation of Sulf2 reduced the expression of CXCL8-induced AT1 R and abrogated the additive effect of CXCL8 on Ang II-induced AT1 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 AT1 R pathway in SHR VSMCs. These findings suggest that Sulf2 is an up-regulatory factor in the additive action of CXCL8 via the AT1 R pathway on Ang II-induced ET-1 expression in VSMCs under hypertension environment.
- Subjects :
- Male
musculoskeletal diseases
0301 basic medicine
medicine.medical_specialty
Small interfering RNA
Vascular smooth muscle
Myocytes, Smooth Muscle
Immunology
Down-Regulation
Biochemistry
Muscle, Smooth, Vascular
Receptor, Angiotensin, Type 1
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Rats, Inbred SHR
Internal medicine
Gene expression
medicine
Animals
Immunology and Allergy
RNA, Messenger
Receptor
Molecular Biology
Angiotensin II receptor type 1
Endothelin-1
Chemistry
Angiotensin II
Interleukin-8
Hematology
musculoskeletal system
Endothelin 1
030104 developmental biology
Endocrinology
030220 oncology & carcinogenesis
cardiovascular system
Sulfotransferases
Endothelin receptor
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 10434666
- Volume :
- 114
- Database :
- OpenAIRE
- Journal :
- Cytokine
- Accession number :
- edsair.doi.dedup.....c0d1c757dcdfe573548b886aa318c8b4