Weak response of bovine hepcidin induction to iron through decreased expression of Smad4.
BMP
Smad4
TGF-β
calf
hepcidin
iron-deficiency anemia
transcription
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
31
08
2023
received:
14
06
2023
accepted:
25
09
2023
medline:
27
10
2023
pubmed:
6
10
2023
entrez:
6
10
2023
Statut:
ppublish
Résumé
Hepcidin negatively regulates systemic iron levels by inhibiting iron entry into the circulation. Hepcidin production is increased in response to an increase in systemic iron via the activation of the bone morphogenetic protein (BMP) pathway. Regulation of hepcidin expression by iron status has been proposed on the basis of evidence mainly from rodents and humans. We evaluated the effect of iron administration on plasma hepcidin concentrations in calves and the expression of bovine hepcidin by the BMP pathway in a cell culture study. Hematocrit as well as levels of blood hemoglobin and plasma iron were lower than the reference level in calves aged 1-4 weeks. Although intramuscular administration of iron increased iron-related parameters, plasma hepcidin concentrations were unaffected. Treatment with BMP6 increased hepcidin expression in human liver-derived cells but not in bovine liver-derived cells. A luciferase-based reporter assay revealed that Smad4 was required for hepcidin reporter transcription induced by Smad1. The reporter activity of hepcidin was lower in the cells transfected with bovine Smad4 than in those transfected with murine Smad4. The lower expression levels of bovine Smad4 were responsible for the lower activity of the hepcidin reporter, which might be due to the instability of bovine Smad4 mRNA. In fact, the endogenous Smad4 protein levels were lower in bovine cells than in human and murine cells. Smad4 also confers TGF-β/activin-mediated signaling. Induction of TGF-β-responsive genes was also lower after treatment with TGF-β1 in bovine hepatocytes than in human hepatoma cells. We revealed the unique regulation of bovine hepcidin expression and the characteristic TGF-β family signaling mediated by bovine Smad4. The present study suggests that knowledge of the regulatory expression of hepcidin as well as TGF-β family signaling obtained in murine and human cells is not always applicable to bovine cells.
Identifiants
pubmed: 37800888
doi: 10.1096/fj.202301186RR
doi:
Substances chimiques
Hepcidins
0
Smad4 Protein
0
Iron
E1UOL152H7
Bone Morphogenetic Proteins
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23243Informations de copyright
© 2023 Federation of American Societies for Experimental Biology.
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