کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3294856 1209847 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bone Morphogenetic Protein Signaling Is Impaired in an Hfe Knockout Mouse Model of Hemochromatosis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Bone Morphogenetic Protein Signaling Is Impaired in an Hfe Knockout Mouse Model of Hemochromatosis
چکیده انگلیسی

Background and AimsMutations in HFE are the most common cause of the iron-overload disorder hereditary hemochromatosis. Levels of the main iron regulatory hormone, hepcidin, are inappropriately low in hereditary hemochromatosis mouse models and patients with HFE mutations, indicating that HFE regulates hepcidin. The bone morphogenetic protein 6 (BMP6)–SMAD signaling pathway is an important endogenous regulator of hepcidin expression. We investigated whether HFE is involved in BMP6–SMAD regulation of hepcidin expression.MethodsThe BMP6–SMAD pathway was examined in Hfe knockout (KO) mice and in wild-type (WT) mice as controls. Mice were placed on diets of varying iron content. Hepcidin induction by BMP6 was examined in primary hepatocytes from Hfe KO mice; data were compared with those of WT mice.ResultsLiver levels of Bmp6 messenger RNA (mRNA) were higher in Hfe KO mice; these were appropriate for the increased hepatic levels of iron in these mice, compared with WT mice. However, levels of hepatic phosphorylated Smad 1/5/8 protein (an intracellular mediator of Bmp6 signaling) and Id1 mRNA (a target gene of Bmp6) were inappropriately low for the body iron burden and Bmp6 mRNA levels in Hfe KO, compared with WT mice. BMP6 induction of hepcidin expression was reduced in Hfe KO hepatocytes compared with WT hepatocytes.ConclusionsHFE is not involved in regulation of BMP6 by iron, but does regulate the downstream signals of BMP6 that are triggered by iron.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 137, Issue 4, October 2009, Pages 1489–1497
نویسندگان
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