دورية أكاديمية
Involvement of hepcidin in iron metabolism dysregulation in Gaucher disease
العنوان: | Involvement of hepcidin in iron metabolism dysregulation in Gaucher disease |
---|---|
المؤلفون: | Thibaud Lefebvre, Niloofar Reihani, Raed Daher, Thierry Billette de Villemeur, Nadia Belmatoug, Christian Rose, Yves Colin-Aronovicz, Hervé Puy, Caroline Le Van Kim, Mélanie Franco, Zoubida Karim |
المصدر: | Haematologica, Vol 103, Iss 4 (2018) |
بيانات النشر: | Ferrata Storti Foundation, 2018. |
سنة النشر: | 2018 |
المجموعة: | LCC:Diseases of the blood and blood-forming organs |
مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
الوصف: | Gaucher disease (GD) is an inherited deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in tissues such as the spleen, liver, and bone marrow. The resulting lipid-laden macrophages lead to the appearance of “Gaucher cells”. Anemia associated with an unexplained hyperferritinemia is a frequent finding in GD, but whether this pathogenesis is related to an iron metabolism disorder has remained unclear. To investigate this issue, we explored the iron status of a large cohort of 90 type I GD patients, including 66 patients treated with enzyme replacement therapy. Ten of the patients treated with enzyme replacement were followed up before and during treatment. Serum levels of hepcidin, the iron regulatory peptide, remained within the physiological range, while the transferrin saturation was slightly decreased in children. Inflammation-independent hyperferritinemia was found in 65% of the patients, and Perl’s staining of the spleen and marrow smear revealed iron accumulation in Gaucher cells. Treated patients exhibited reduced hyperferritinemia, increased transferrin saturation and transiently increased systemic hepcidin. In addition, the hepcidin and ferritin correlation was markedly improved, and, in most patients, the hemoglobin level was normalized. To further explore eventual iron sequestration in macrophages, we produce a Gaucher cells model by treating the J774 macrophage cell line with a glucocerebrosidase inhibitor and showed induced local hepcidin and membrane retrieval of the iron exporter, ferroportin. These data reveal the involvement of Gaucher cells in abnormal iron sequestration, which may explain the mechanism of hyperferritinemia in GD patients. Local hepcidin-ferroportin interaction was involved in this pathogenesis. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 0390-6078 1592-8721 |
Relation: | https://haematologica.org/article/view/8412; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
DOI: | 10.3324/haematol.2017.177816 |
URL الوصول: | https://doaj.org/article/1022b410de7d4b8d9c24db00fa464243 |
رقم الأكسشن: | edsdoj.1022b410de7d4b8d9c24db00fa464243 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 03906078 15928721 |
---|---|
DOI: | 10.3324/haematol.2017.177816 |