β3-adrenergic receptor activation induces TGFβ1 expression in cardiomyocytes via the PKG/JNK/c-Jun pathway

In heart failure, the expression of cardiac β3-adrenergic receptors (β3-ARs) increases. However, the precise role of β3-AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the pro...

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Published in:Biochemical and biophysical research communications 2018-09, Vol.503 (1), p.146-151
Main Authors: Xu, Zhongcheng, Wu, Jimin, Xin, Junzhou, Feng, Yenan, Hu, Guomin, Shen, Jing, Li, Mingzhe, Zhang, Youyi, Xiao, Han, Wang, Li
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
c-Jun
c-Jun N-Terminal kinase
Cardiomyocyte
HEART FAILURE
LYMPHOKINES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
Protein kinase G
RATS
RECEPTORS
SYMPATHOMIMETICS
Transforming growth factor β1
β3-adrenergic receptor
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Summary:In heart failure, the expression of cardiac β3-adrenergic receptors (β3-ARs) increases. However, the precise role of β3-AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) 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 β3-AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β3-AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β3-AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a β3-AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGFβ1 expression upon β3-AR activation. A protein kinase G (PKG) inhibitor also attenuated β3-AR-agonist-induced TGFβ1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the β3-AR activation in cardiomyocytes increases the expression of TGFβ1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of β3-AR signaling in heart failure. [Display omitted] •β3-AR activation increased TGFβ1 expression in neonatal rat cardiomyocytes.•JNK-activated c-Jun mediated TGFβ1 transcription induced by β3-AR activation.•PKG signaling of β3-AR induced JNK/c-Jun activation and TGFβ1 expression.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.05.200