The hemochromatosis protein HFE signals predominantly via the BMP type I receptor ALK3 in vivo

Lisa Traeger, Caroline Enns, Jan Krijt, Andrea U. Steinbicker

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Mutations in HFE, the most common cause of hereditary hemochromatosis, lead to iron overload. The iron overload is characterized by increased iron uptake due to lower levels of the hepatic, iron regulatory hormone hepcidin. HFE was cloned 21 years ago, but the signaling pathway is still unknown. Because bone morphogenetic protein (BMP) signaling is impaired in patients with hereditary hemochromatosis, and the interaction of HFE and the BMP type I receptor ALK3 was suggested in vitro, in vivo experiments were performed. In vivo, hepatocyte-specific Alk3-deficient and control mice were injected with either AAV2/8-Hfe-Flag or PBS. HFE overexpression in control mice results in increased hepatic hepcidin levels, p-Smad1/5 levels, and iron deficiency anemia, whereas overexpression of HFE in hepatocyte-specific Alk3-deficient mice results in no change in hepcidin, p-Smad1/5 levels, or blood parameters. These results indicate that HFE signals predominantly via ALK3 to induce hepcidin in vivo.

Original languageEnglish (US)
Article number65
JournalCommunications Biology
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2018

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Type I Bone Morphogenetic Protein Receptors
hemochromatosis
Hepcidins
bone morphogenetic proteins
Iron
iron overload
receptors
Iron Overload
Hemochromatosis
hepatocytes
Hepatocytes
mice
Proteins
proteins
iron
liver
iron deficiency anemia
Bone Morphogenetic Proteins
Iron-Deficiency Anemias
Liver

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

The hemochromatosis protein HFE signals predominantly via the BMP type I receptor ALK3 in vivo. / Traeger, Lisa; Enns, Caroline; Krijt, Jan; Steinbicker, Andrea U.

In: Communications Biology, Vol. 1, No. 1, 65, 01.12.2018.

Research output: Contribution to journalArticle

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