1. The type I BMP receptor Alk3 is required for the induction of hepatic hepcidin gene expression by interleukin-6.
- Author
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Mayeur, Claire, Lohmeyer, Lisa K., Leyton, Patricio, Kao, Sonya M., Pappas, Alexandra E., Kolodziej, Starsha A., Spagnolli, Ester, Binglan Yu, Galdos, Rita L., Yu, Paul B., Peterson, Randall T., Bloch, Donald B., Bloch, Kenneth D., and Steinbicker, Andrea U.
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PHOSPHORYLATION , *HEPCIDIN , *ANEMIA , *INTERLEUKIN-6 , *GENE expression - Abstract
Increased IL-6 production induces, via STAT3 phosphorylation, hepatic transcription of the gene encoding the iron-regulatory hormone, hepcidin, leading to development of anemia of chronic disease (ACD). Inhibition of bone morphogenetic protein (BMP) signaling prevents the induction of hepcidin gene expression by IL-6 and ameliorates ACD. Using mice with hepatocyte-specific deficiency of Alk2 or Alk3, we sought to identify the BMP type I receptor that participates in IL-6-mediated induction of hepcidin gene expression. Mice were injected with adenovirus specifying IL-6 (Ad.IL-6) or control adenovirus. Seventy-two hours later, serum iron concentrations and hepatic levels of STAT3 phosphorylation and hepcidin messenger RNA were measured. Additional mice were injected with recombinant murine IL-6 (mIL-6) or vehicle, and hepatic hepcidin gene expression was measured 4 hours later. Deficiency of Alk2 or Alk3 did not alter the ability of Ad.IL-6 injection to induce hepatic STAT3 phosphorylation. Ad.IL-6 increased hepatic hepcidin messenger RNA levels and decreased serum iron concentrations in Alk2- but not Alk3-deficient mice. Similarly, administration of mIL-6 induced hepatic hepcidin gene expression in Alk2- but not Alk3-deficient mice. These results demonstrate that the ability of IL-6 to induce hepatic hepcidin gene expression and reduce serum iron concentrations is dependent on the BMP type I receptor Alk3. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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