Increased Iron Loading Induces Bmp6 Expression in the Non-Parenchymal Cells of the Liver Independent of the BMP-Signaling Pathway |
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| Authors: | Caroline A. Enns Riffat Ahmed Jiaohong Wang Akiko Ueno Christal Worthen Hidekazu Tsukamoto An-Sheng Zhang |
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| Affiliation: | 1. Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon, United States of America.; 2. Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America.; 3. Department of Veteran Affairs, Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.; Baylor College of Medicine, United States of America, |
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| 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. |
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