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Published on: February 10, 2015
Iron overload induces BMP6 expression in the liver but not in the duodenum
Léon Kautz1, Céline Besson-Fournier, Delphine Meynard
1Inserm U563, Université de Toulouse, F-31024 Toulouse, France.
Background:
The bone morphogenetic protein BMP6 regulates hepcidin production by the liver. However, it is not yet known whether BMP6 derives from the liver itself or from other sources such as the small intestine, as has been recently suggested. This study was aimed at investigating the source of BMP6 further.
Design And Methods:
We used three different strains of mice (C57BL/6, DBA/2, and 129/Sv) with iron overload induced either by an iron-enriched diet or by inactivation of the Hfe gene. We examined Bmp6 expression at both the mRNA (by quantitative PCR) and protein (by immunohistochemistry and Western blotting analyses) levels.
Results:
We showed that iron overload induces Bmp6 mRNA expression in the liver but not in the duodenum of these mice. Bmp6 is also detected by immunohistochemistry in liver tissue sections of mice with iron overload induced either by an iron-enriched diet or by inactivation of the Hfe gene, but not in liver tissue sections from iron-loaded Bmp6-deficient mice. Bmp6 in the duodenum was below immunodetection threshold, thus confirming quantitative PCR data. Lack of specificity of available antibodies together with slight heterogeneity between 129 substrains may account for the differences with previously published data.
Conclusions:
Our data strongly support the importance of liver BMP6 for regulation of iron metabolism. Indeed, they demonstrate that intestinal Bmp6 expression is modulated by iron neither at the mRNA nor at the protein level.
Insights
Liver bone morphogenetic protein 6 (BMP6) is crucial for iron metabolism regulation. This study demonstrates that BMP6 originates from the liver, not the intestine, in response to iron overload.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Bone morphogenetic protein 6 (BMP6) regulates hepcidin production, a key protein in iron metabolism.
- The primary source of BMP6, whether hepatic or intestinal, remains debated.
Purpose of the Study:
- To investigate the origin of BMP6 in the context of iron overload.
- To determine if the small intestine contributes to BMP6 production.
Main Methods:
- Utilized three mouse strains (C57BL/6, DBA/2, 129/Sv) with induced iron overload (iron-rich diet or Hfe gene inactivation).
- Assessed Bmp6 gene and protein expression in liver and duodenum using quantitative PCR, immunohistochemistry, and Western blotting.
Main Results:
- Iron overload increased Bmp6 mRNA and protein expression in the liver.
- Bmp6 expression in the duodenum was not significantly modulated by iron overload at either the mRNA or protein level.
- Immunodetection of BMP6 in the duodenum was below the threshold, supporting quantitative PCR findings.
Conclusions:
- Hepatic BMP6 is essential for regulating iron metabolism.
- Intestinal BMP6 expression is not significantly influenced by iron levels, refuting the hypothesis of intestinal origin.
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