The gp130/STAT3 signaling pathway mediates beta-adrenergic receptor-induced atrial natriuretic factor expression in cardiomyocytes.
beta-Adrenergic receptor (beta-AR)-induced cardiac remodeling is closely linked with the re-expression of the atrial natriuretic factor (ANF) gene. However, the exact molecular mechanism of this response remains elusive. Here, we demonstrate that the beta-AR agonist isoproterenol potently evokes the tyrosine phosphorylation of STAT3 and increases its transcriptional activity in an extracellularly regulated kinase 1/2 and glycoprotein (gp)130 signaling-dependent manner in rat cardiomyocytes. Interestingly, both specific silencing of signal transducers and activators of transcription 3 (STAT3) expression by lentivirus-mediated RNA interference and antagonism of gp130 signaling lead to significant inhibition of isoproterenol-stimulated ANF expression. Together, these results indicate that gp130/STAT3 signaling has an essential role in ANF expression by beta-AR stimulation.
Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
Hui
H
Zhang
Wei
W
Feng
Wenqiang
W
Liao
Xiaowei
X
Ma
Qide
Q
Han
Youyi
Y
Zhang
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D015870:Gene Expression; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D016207:Cytokines; D011943:Receptors, Adrenergic, beta; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D009320:Atrial Natriuretic Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D007545:Isoproterenol