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Hepatocyte growth factor (HGF) suppresses hepcidin expression in hepatocytes by interfering with BMP‐mediated hepcidin induction
Author(s) -
Goodnough Julia,
Nemeth Elizabeta,
Ganz Tomas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.974.2
Subject(s) - hepcidin , hepatocyte growth factor , small interfering rna , chemistry , luciferase , transfection , endocrinology , medicine , hepatocyte , microbiology and biotechnology , cancer research , biology , receptor , in vitro , inflammation , biochemistry , gene
Hepcidin, a 25‐amino‐acid peptide synthesized in the liver, is the iron regulatory hormone. Suppression of hepcidin in the setting of anemia appears to depend on a soluble factor expressed in the bone marrow during erythropoiesis. Here we describe that hepatocyte growth factor (HGF) suppresses hepcidin mRNA in a dose‐response fashion, in the concentration range detected in human serum. A similar response is observed in primary cells or cell lines transfected with a hepcidin promoter‐luciferase reporter. HGF is a ligand for the receptor tyrosine kinase (RTK), Met. In HepG2 cells transfected with the hepcidin‐luciferase reporter, the luminescence is specifically suppressed by HGF and not other ligands of RTKs, PDGF and EGF. BMPs 2, 4, 6 and 9 are strong inducers of hepcidin, and the BMP2/4 pathway also mediates hepcidin induction by iron‐transferrin. We report that HGF prevents a BMP2‐mediated increase in hepcidin mRNA and the activity of the luciferase reporter. HGF also prevented the induction by BMP2 of an unrelated BMP‐sensitive luciferase reporter. In primary hepatocytes, the BMP‐sensitive transcript ID1 is also downregulated by HGF. Thus, HGF may be a novel suppressor of hepcidin, modulating hepcidin expression by interfering with BMP signaling. We speculate that HGF could mediate the suppression of hepcidin in chronic liver diseases. This research is supported by National Institutes of Health grant #1F30DK082151.