The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo

An-Sheng Zhang, Junwei Gao, Dwight D. Koeberl, Caroline Enns

Research output: Contribution to journalArticle

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Abstract

Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv-/-) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv-/- mice do not lack BMP6. Furthermore, iron depletion in Hjv -/- mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv-/- mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling.

Original languageEnglish (US)
Pages (from-to)16416-16423
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number22
DOIs
StatePublished - May 28 2010

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Hepcidins
Hepatocytes
Bone
Bone and Bones
Liver
Proteins
Iron
Messenger RNA
Bone Morphogenetic Protein Receptors
Iron Overload
Peptide Hormones
Small Intestine
Muscle
Myocardium
Animals
Skeletal Muscle
Homeostasis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo. / Zhang, An-Sheng; Gao, Junwei; Koeberl, Dwight D.; Enns, Caroline.

In: Journal of Biological Chemistry, Vol. 285, No. 22, 28.05.2010, p. 16416-16423.

Research output: Contribution to journalArticle

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