title: Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels.
abstract: BACKGROUND
  Considering 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.
  
  
  METHODS
  Male 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.
  
  
  RESULTS
  Vitamin 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Postgraduate Program in Human Nutrition, Faculty of Health Sciences, University of Brasília, Campus Universitário Darcy Ribeiro, POBox 70910-900, Brasília, DF Brazil ; Instituto de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Bioquímica da Nutrição, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Bloco J, 1 Andar. Asa Norte, Brasília, Distrito Federal CEP: 70910-900 Brasil.
authors.forename: Juliana Frossard Ribeiro
authors.initials: JF
authors.lastname: Mendes
authors.affiliation: Cell Biology Department of Biological Sciences Institute, University of Brasília, Campus Universitário Darcy Ribeiro, POBox 70910-900, Brasília, DF Brazil.
authors.forename: Egle Machado de Almeida
authors.initials: EM
authors.lastname: Siqueira
authors.affiliation: Nutrition Department of Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, POBox 70910-900, Brasília, DF Brazil.
authors.forename: João Gabriel Marques
authors.initials: JG
authors.lastname: de Brito E Silva
authors.affiliation: Postgraduate Program in Human Nutrition, Faculty of Health Sciences, University of Brasília, Campus Universitário Darcy Ribeiro, POBox 70910-900, Brasília, DF Brazil ; Instituto de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Bioquímica da Nutrição, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Bloco J, 1 Andar. Asa Norte, Brasília, Distrito Federal CEP: 70910-900 Brasil.
authors.forename: Sandra Fernandes
authors.initials: SF
authors.lastname: Arruda
keywords: Bone morphogenetic protein 6; Hemojuvelin; Hepcidin; Iron status; Vitamin A deficiency