3 years ago

The α1-adrenergic receptor is involved in hepcidin upregulation induced by adrenaline and norepinephrine via the STAT3 pathway

Yanmei Cui, Shu-E Zhao, Yunzhe Ci, Shuqiang Zhao, Lide Xie, Yu-Jian Fu, Yongping Bao, Yuhua Lei, Wei-Na Kong, Yan-Zhong Chang
Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1-adrenergic receptor agonist), prazosin (PZ, α1-adrenergic receptor antagonist), and/or propranolol (Pro, β-adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin-light (Ft-L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 d, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft-L protein and non-heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1-adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26715

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