In heart failure, the expression of cardiac beta(3)-adrenergic receptors (beta(3)-ARs) increases. However, the precise role of beta(3)-AR signaling within cardiomyocytes remains unclear. Transforming growth factor beta 1(TGF beta 1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of beta(3)-AR activation on TGF beta 1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective beta(3)-AR agonist BRL37344 induced an increase in TGF beta 1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in beta(3)-AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a beta(3)-AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGF beta 1 expression upon beta(3)-AR activation. A protein kinase G (PKG) inhibitor also attenuated beta(3)-AR-agonist-induced TGF beta 1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the beta(3)-AR activation in cardiomyocytes increases the expression of TGF beta 1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of beta(3)-AR signaling in heart failure. (C) 2018 Elsevier Inc. All rights reserved.