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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 / 영남의대학술지
Yeungnam University Journal of Medicine ; : 43-54, 2017.
Artículo en Inglés | WPRIM | ID: wpr-787050
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.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Ratas Endogámicas SHR / Sulfatasas / Araquidonato 12-Lipooxigenasa / ARN Mensajero / Angiotensina II / Angiotensinas / Regulación hacia Abajo / Western Blotting / Endotelina-1 / Proteoglicanos de Heparán Sulfato Idioma: Inglés Revista: Yeungnam University Journal of Medicine Año: 2017 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Ratas Endogámicas SHR / Sulfatasas / Araquidonato 12-Lipooxigenasa / ARN Mensajero / Angiotensina II / Angiotensinas / Regulación hacia Abajo / Western Blotting / Endotelina-1 / Proteoglicanos de Heparán Sulfato Idioma: Inglés Revista: Yeungnam University Journal of Medicine Año: 2017 Tipo del documento: Artículo