Abstract
Bone morphogenetic protein 6 (BMP6) is an essential cytokine for the expression of hepcidin, an iron regulatory hormone secreted predominantly by hepatocytes. Bmp6 expression is upregulated by increased iron-levels in the liver. Both hepatocytes and non-parenchymal liver cells have detectable Bmp6 mRNA. Here we showed that induction of hepcidin expression in hepatocytes by dietary iron is associated with an elevation of Bmp6 mRNA in the non-parenchymal cells of the liver. Consistently, incubation with iron-saturated transferrin induces Bmp6 mRNA expression in isolated hepatic stellate cells, but not in hepatocytes. These observations suggest an important role of the non-parenchymal liver cells in regulating iron-homeostasis by acting as a source of Bmp6.
Highlights
Systemic iron homeostasis is maintained by tightly regulating the expression of hepcidin, a peptide hormone predominantly secreted by hepatocytes, via an elegant but poorly defined mechanism
We previously showed the expression of Bone morphogenetic protein 6 (BMP6) mRNA in the non-parenchymal liver cells (NPCs) including sinusoidal endothelial cells (SECs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) as well as in hepatocytes [16]
Hemojuvelin knockout (Hjv-/-) mice had low levels of hepatic hepcidin expression resulting in severe iron overload and an approximately 2.7-fold elevation of Bmp6 mRNA expression in the liver, when compared with the corresponding wild-type counterparts (Fig. 1A-D)
Summary
Systemic iron homeostasis is maintained by tightly regulating the expression of hepcidin, a peptide hormone predominantly secreted by hepatocytes, via an elegant but poorly defined mechanism. Hepcidin negatively controls the efflux of iron out of the intestinal epithelial cells, macrophages and hepatocytes by binding to and inducing the down-regulation of ferroportin, the only known iron exporter [1,2]. High levels of hepcidin result in iron accumulation in macrophages and hepatocytes and a lack of iron export from the intestinal epithelial cells into the blood stream, which lead to iron deficiency anemia [3]. BMP6 induces hepcidin expression by binding to specific BMP receptors and the coreceptor hemojuvelin (HJV) in hepatocytes via the BMP-signaling pathway [8,9]. In this study we find that the non-parenchymal cells rather than hepatocytes, respond to increased iron levels by increasing BMP6 mRNA. Induction of BMP6 mRNA in NPCs is independent of BMP signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
