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In April 2001, a team of researchers from
the Institut Cochin (Unit 567 of INSERM, Joint Research Unit 8104 of the
CNRS, Université René Descartes), in partnership with researchers
from the INSERM Unit 409, "Molecular Pathology and Genetics of Hematopoiesis"
(Hôpital Bichat, Paris), set forth the hypothesis that hepcidin,
a peptidic molecule, that is, a molecule composed of a series of amino
acids, synthesized by the liver, was the main hormone involved in the
regulation of iron homeostasis in the organism.
Since that time, this hypothesis has been largely
confirmed, by this team and other researchers throughout the world. It
was especially demonstrated that hepcidin was involved in the mechanism
of major illnesses related to iron homeostasis, inflammatory anemia and
iron overload. Inflammatory anemia is a complication in many illnesses
such as rheumatism and cancer, and seems to be due to an excessive secretion
of hepcidin.
Iron overload can be secondary to chronic anemia or the cause. In this
case, we speak of hereditary hemochromatosis. This is the most common
of all the genetic illnesses, afflicting almost one person out of 200
to 300. The main cause of hereditary hemochromatosis is the mutation of
the HFE gene located on chromosome 6. Patients will have inherited a mutated
version of the gene from each of their parents.
Until this year, we did not understand the mechanism leading to the digestive
hyperabsorption of iron in patients.
In a recent article published in the journal, Nature Genetics (on line),
Gaël Nicolas and his co-workers (Dr. Sophie Vaulont's team at the
Institut Cochin, headed by Axel Kahn, in association with the INSERM Unit
409 at the Hôpital Bichat, and the team led by Nancy Andrews, researcher
at the Howard Hughes Medical Institute in Boston, MS, USA), showed that
mice with an Hfe protein deficiency and, therefore, human hemochromatosis
models, have a decreased production of hepcidin that could explain this
iron overload. As a result, the induction of hepcidin hyperproduction
in mice through the introduction of a transgene totally prevents iron
overload (1).
Very recent results from Australian researchers suggest that these data
are also valid for this illness in humans.
In conclusion, the discovery of the role of hepcidin by French researchers
in 2001 has led to a scientific revolution in the field of iron homeostasis
and its related illnesses. We are sure at this time that hepcidin plays
a major role in all of these phenomena, whether they be physiological
or pathological.
Hereditary hemochromatosis, the most common of these genetic illnesses,
generally seems to be due to an insufficient secretion of hepcidin. It
follows that treatment of patients with hepcidin, its analogues or products
that increase iron synthesis should be the basis of a logical preventive
treatment of this disease in the future.
On line:
http://www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/vaop/ncurrent/index.html
Notes:
(1) Gaël Nicolas, Lydie Viatte, Dan-Qing Lou, Myriam Bennoun, Carole
Beaumont, Axel Kahn, Nancy C. Andrews and Sophie Vaulont. Constitutive
hepcidin expression prevents iron overload in a mouse model of hemochromatosis,
Nature Genetics, 2003.
Contacts:
Sophie Vaulont
Institut COCHIN – Département GDPM
Tel: +33 1 44 41 24 47
E-mail: vaulont@cochin.inserm.fr
Axel Kahn
Institut COCHIN – Direction
Tel: +33 1 40 51 64 57
E-mail: kahn@cochin.inserm.fr
Marie-Pascale Corneloup
Institut COCHIN – Communication
Tel: +33 1 40 51 64 85
E-mail: corneloup@cochin.inserm.fr
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