Calcineurin/NFAT signaling pathway mediates endothelin-1-induced pulmonary artery smooth muscle cell proliferation by regulating phosphodiesterase-5 / 南方医科大学学报
Journal of Southern Medical University
;
(12): 26-29, 2013.
Artigo
em Chinês
| WPRIM
| ID: wpr-352315
ABSTRACT
<p><b>OBJECTIVE</b>To examine whether calcineurin/NFAT signaling pathway mediates endothelin-1 (ET-1)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating phosphodiesterase-5 (PDE5) and the effect of the selective calcineurin inhibitor cyclosporine A and PDE5 inhibitor sildenafil on ET-1-induced PASMC proliferation.</p><p><b>METHODS</b>PASMCs were treated with ET-1 to stimulate their proliferation with or without prior treatment of the cells with CsA or sildenafil. Calcineurin activity in the cells was measured using a calcineurin activity assay kit, PDE5 expression examined using immunoblotting, and cGMP level detected using a cGMP direct immunoassay kit. PASMC proliferation following the treatments was determined using [(3)H]thymidine incorporation assay.</p><p><b>RESULTS</b>ET-1 caused a 2.05-fold increase in the cellular calcineurin activity, a 1.80-fold increase in PDE5 expression, and a 3.20-fold increase in the DNA synthesis rate, and reduced the cGMP level by 67%. Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Both Cyclosporine and sildenafil suppressed ET-1-stimulated PASMC proliferation.</p><p><b>CONCLUSION</b>Activation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Both Cyclosporine and sildenafil can suppress ET-1-stimulated PASMC proliferation in vitro.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Piperazinas
/
Artéria Pulmonar
/
Purinas
/
Sulfonas
/
DNA
/
Transdução de Sinais
/
Células Cultivadas
/
Ciclosporina
/
Ratos Sprague-Dawley
Limite:
Animais
Idioma:
Chinês
Revista:
Journal of Southern Medical University
Ano de publicação:
2013
Tipo de documento:
Artigo
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