海西定
SMAD公司
骨形态发生蛋白6
信号转导
内分泌学
内科学
骨形态发生蛋白
细胞生物学
生物
医学
骨形态发生蛋白7
生物化学
炎症
基因
作者
Elena Corradini,Delphine Meynard,Qiming Wu,Shan Chen,Paolo Ventura,Antonello Pietrangelo,Jodie L. Babitt
出处
期刊:Hepatology
[Wiley]
日期:2011-06-24
卷期号:54 (1): 273-284
被引量:168
摘要
The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is a central regulator of hepcidin expression and systemic iron balance. However, the molecular mechanisms by which iron is sensed to regulate BMP6-SMAD signaling and hepcidin expression are unknown. Here we examined the effects of circulating and tissue iron on Bmp6-Smad pathway activation and hepcidin expression in vivo after acute and chronic enteral iron administration in mice. We demonstrated that both transferrin saturation and liver iron content independently influence hepcidin expression. Although liver iron content is independently positively correlated with hepatic Bmp6 messenger RNA (mRNA) expression and overall activation of the Smad1/5/8 signaling pathway, transferrin saturation activates the downstream Smad1/5/8 signaling cascade, but does not induce Bmp6 mRNA expression in the liver. Hepatic inhibitory Smad7 mRNA expression is increased by both acute and chronic iron administration and mirrors overall activation of the Smad1/5/8 signaling cascade. In contrast to the Smad pathway, the extracellular signal-regulated kinase 1 and 2 (Erk1/2) mitogen-activated protein kinase (Mapk) signaling pathway in the liver is not activated by acute or chronic iron administration in mice.Our data demonstrate that the hepatic Bmp6-Smad signaling pathway is differentially activated by circulating and tissue iron to induce hepcidin expression, whereas the hepatic Erk1/2 signaling pathway is not activated by iron in vivo.
科研通智能强力驱动
Strongly Powered by AbleSci AI