Abstract
BackgroundConsidering that vitamin A deficiency modulates hepcidin expression and consequently affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway.MethodsMale Wistar rats were treated: control AIN-93G diet (CT), vitamin A-deficient diet (VAD), iron-deficient diet (FeD), vitamin A- and iron-deficient diet (VAFeD), or 12 mg all-trans retinoic acid (atRA)/kg diet.ResultsVitamin A deficiency (VAD) increased hepatic Bmp6 and Hfe2 mRNA levels and down-regulated hepatic Hamp, Smad7, Rarα, and intestinal Fpn1 mRNA levels compared with the control. The FeD rats showed lower hepatic Hamp, Bmp6, and Smad7 mRNA levels compared with those of the control, while in the VAFeD rats only Hamp and Smad7 mRNA levels were lower than those of the control. The VAFeD diet up-regulated intestinal Dmt1 mRNA levels in relation to those of the control. The replacement of retinyl ester by atRA did not restore hepatic Hamp mRNA levels; however, the hepatic Hfe2, Bmp6, and Smad7 mRNA levels were similar to the control. The atRA rats showed an increase of hepatic Rarα mRNA levels and a reduction of intestinal Dmt1 mRNA and Fpn1 levels compared with those of the control.ConclusionsThe HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in iron deficiency is impaired by vitamin A deficiency despite increased expression of liver Bmp6 and Hfe2 mRNA levels and decreased expression of Smad7 mRNA. This response may be associated to the systemic iron deficiency and spleen iron retention promoted by vitamin A deficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0519-4) contains supplementary material, which is available to authorized users.
Highlights
Considering that vitamin A deficiency modulates hepcidin expression and affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway
The consumption of all-trans retinoic acid (atRA), as the only source of dietary vitamin A, resulted in mRNA levels of Hfe2, bone morphogenetic protein 6 (Bmp6), and SMAD family member 7 (Smad7) be similar to those values obtained in the control group; the atRA diet failed to reverse the inhibitory effect of vitamin A deficiency on Hamp mRNA levels (2.8-fold, p = 0.002) in the liver
The vitamin A- and iron-deficient diet (VAFeD) group showed lower hepatic levels of Hamp and Smad7 mRNA (12.6-fold and 2.4-fold, p = 0.000 and 0.006, respectively) relative to the control group, but no difference was observed in the Hfe2 and Bmp6 mRNA levels, between these two groups
Summary
Considering that vitamin A deficiency modulates hepcidin expression and affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway. A peptide hormone secreted by the liver, is an essential molecule for systemic iron homeostasis regulation. The primary role of hepcidin is to control the amount of iron that is released into the circulation from enterocytes and spleen macrophages. The result is the prevention of the iron release from enterocytes and splenic macrophages. Hepcidin gene expression is Mendes et al Genes & Nutrition (2016) 11:1 regulated by several factors, including body iron status, inflammation, erythropoiesis, and hypoxia (Evstatiev and Gasche 2012)
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