title: Organ specificity of beta-carotene induced lung gene-expression changes in Bcmo1-/- mice.
abstract: METHODS
  Whole genome transcriptome analysis of male and female beta-carotene 15,15'-monooxygenase knockout (Bcmo1(-/-) ) and Bcmo1(+/+)  (wild-type) mice with or without 14 wk of BC supplementation was done. We previously showed that only 1.8% of the genes regulated by BC in lung were also regulated in liver and inguinal white adipose tissue (iWAT), suggesting lung specific responses. Here, we explicitly questioned the lung specificity.
  
  
  RESULTS
  We show that BC supplementation resulted in an opposite direction of gene-regulation in male compared to female Bcmo1(-/-)  mice in lung, liver, and iWAT. This supports a systemic effect of BC on steroid hormone metabolism mediated responses. Lung, liver, and iWAT of female Bcmo1(-/-)  mice showed an increased inflammatory response, which was counteracted by supplementation of BC. This supports a genotype dependent increased sensitivity of female mice for vitamin A deficiency. Finally, the effect of BC on Wnt signaling in male Bcmo1(-/-)  mice was examined. Frizzled homolog 6 (Fzd6) downregulation was seen in all three tissues. Collagen triple helix containing 1 (Cthrc1) downregulation was seen in lung tissue only, suggesting specificity. Upregulation of genes involved in oxygen sensing was seen in lung and iWAT, while protocadherin upregulation was only seen in lung.
  
  
  CONCLUSIONS
  Our results demonstrate that effects of BC are strongly sex dependent. While effects of BC on hormone metabolism mediated responses and inflammation are systemic, effects on Wnt signaling may be lung specific.
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Yvonne G J
authors.initials: YG
authors.lastname: van Helden
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009928:Organ Specificity / Q000187:drug effects; D012737:Sex Factors; D015854:Up-Regulation; D014802:Vitamin A Deficiency / Q000235:genetics / Q000503:physiopathology; D060449:Wnt Signaling Pathway; D019207:beta Carotene / Q000008:administration & dosage* / Q000097:blood; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: C530500:Cthrc1 protein, mouse; D016326:Extracellular Matrix Proteins; D051157:Frizzled Receptors; C111048:Fzd6 protein, mouse; D019207:beta Carotene; D050559:beta-Carotene 15,15'-Monooxygenase