Angiotensin II regulates the LARG/RhoA/MYPT1 axis in rat vascular smooth muscle in vitro.
Acta Pharmacol Sin
; 33(12): 1502-10, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-23123644
ABSTRACT
AIM:
To identify a key protein that binds monomeric G protein RhoA and activates the RhoA/Rho kinase/MYPT1 axis in vascular smooth muscle cells (VSMCs) upon angiotensin II (Ang II) stimulation.METHODS:
Primary cultured VSMCs from Sprague-Dawley rats were transfected with siRNAs against leukemia-associated RhoGEF (LARG), and then treated with Ang II, losartan, PD123319, or Val(5)-Ang II. The target mRNA and protein levels were determined using qPCR and Western blot analysis, respectively. Rat aortic rings were isolated, and the isometric contraction was measured with a force transducer and recorder.RESULTS:
Stimulation with Ang II (0.1 µmol/L) for 0.5 h significantly increased the level of LARG mRNA in VSMCs. At 3, 6, and 9 h after the treatment with Ang II (0.1 µmol/L) plus AT(2) antagonist PD123319 (1 µmol/L) or with AT(1) agonist Val(5)-Ang II (1 µmol/L), the LARG protein, RhoA activity, and phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) in VSMCs were significantly increased. Knockdown of LARG with siRNA reduced these effects caused by AT(1) receptor activation. In rat aortic rings pretreated with LARG siRNA, Ang II-induced contraction was diminished.CONCLUSION:
Ang II upregulates LARG gene expression and activates the LARG/RhoA/MYPT1 axis via AT(1), thereby maintaining vascular tone.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Angiotensina II
/
Regulación de la Expresión Génica
/
Proteína de Unión al GTP rhoA
/
Factores de Intercambio de Guanina Nucleótido
/
Proteína Fosfatasa 1
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China