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2014 ; 124
(13
): 2116-23
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BMP type II receptors have redundant roles in the regulation of hepatic hepcidin
gene expression and iron metabolism
#MMPMID25075125
Mayeur C
; Leyton PA
; Kolodziej SA
; Yu B
; Bloch KD
Blood
2014[Sep]; 124
(13
): 2116-23
PMID25075125
show ga
Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is
regulated by bone morphogenetic protein (BMP) signaling. We sought to identify
which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is
responsible for regulating hepcidin gene expression. We studied Bmpr2
heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of
BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes
lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum
hepcidin and iron levels, and tissue iron levels did not differ in wild-type
mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient.
Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene
expression and serum hepcidin levels leading to severe iron overload. Iron
injection increased hepatic hepcidin mRNA levels in mice deficient in either
BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In
addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and
ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression.
These results suggest that BMP type II receptors, BMPR2 and ActR2a, have
redundant roles in the regulation of hepatic hepcidin gene expression and iron
metabolism.
|*Gene Expression Regulation
[MESH]
|Actin-Related Protein 2/deficiency
[MESH]
|Animals
[MESH]
|Bone Morphogenetic Protein Receptors, Type II/deficiency/genetics/*metabolism
[MESH]