Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates hepcidin levels reached after LPS challenge

Chloé Latour; Céline Besson-Fournier; Ophélie Gourbeyre; Delphine Meynard; Marie-Paule Roth; Hélène Coppin

doi:10.1182/blood-2017-07-795658

Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates hepcidin levels reached after LPS challenge: Combined BMP6/HJV deficiency, iron and inflammation

Chloé Latour ¹ Céline Besson-Fournier ¹ Ophélie Gourbeyre ¹ Delphine Meynard ¹ Marie-Paule Roth ^{1, *} Hélène Coppin ^{1, *}

* Auteur correspondant

1 Institut de Recherche en Santé Digestive - IRSD [Purpan, Toulouse]

Abstract : Lack of either BMP6 or the BMP co-receptor hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males. This is consistent with the current views that HJV is a co-receptor for BMP6 in hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin independently of each other, we intercrossed Hjv-/- and Bmp6-/- mice and compared the phenotype of animals of the F2 progeny. Loss of Bmp6 further repressed Smad signaling and hepcidin expression in the liver of Hjv-/- mice of both genders, and led to iron accumulation in the pancreas and the heart of females. These data suggest that, in Hjv-/- females, Bmp6 can provide a signal adequate to maintain hepcidin to a level sufficient to avoid extrahepatic iron loading. We also examined the impact of Bmp6 and/or Hjv deletion on the regulation of hepcidin by inflammation. Our data show that lack of one or both molecules does not prevent induction of hepcidin by LPS. However, BMP/Smad signaling in unchallenged animals is determinant for the level of hepcidin reached after stimulation, which is consistent with a synergy between IL6/STAT3 and BMP/SMAD signaling in regulating hepcidin during inflammation.

Type de document :

Article dans une revue

Blood, American Society of Hematology, In press, Epub ahead of print. 〈10.1182/blood-2017-07-795658〉

Domaine :

Sciences du Vivant [q-bio] / Médecine humaine et pathologie / Hépatologie et Gastroentérologie

Sciences du Vivant [q-bio] / Médecine humaine et pathologie / Hématologie

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Dernière modification le : samedi 15 septembre 2018 - 01:08:46
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Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates hepcidin levels reached after LPS challenge: Combined BMP6/HJV deficiency, iron and inflammation

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Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates hepcidin levels reached after LPS challenge: Combined BMP6/HJV deficiency, iron and inflammation

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