Abgueguen Emmanuelle, Toutain Bertrand, Bédrine Hélène, Chicault Céline, Orhant Magali, Aubry Marc, Monnier Annabelle, Mottier Stéphanie, Jouan Hélène, Bahram Seiamak, Mosser Jean, Fergelot Patricia
CNRS UMR 6061, Université de Rennes1, IFR 140, Faculté de Médecine, CS 34317, 35043 Rennes, France.
Mamm Genome. 2006 May;17(5):430-50. doi: 10.1007/s00335-005-0122-z.
Iron absorption, distribution, use, and storage are thought to be tightly regulated since altered iron stores may lead to cellular damage and disease. HFE, the hereditary hemochromatosis gene product, is expressed in the crypts of the duodenum, but the molecular mechanism by which it contributes to the inhibition of iron absorption is still unknown. In this study we aimed to identify transcriptional profiles in the duodenal epithelium of Hfe(-/-) mice. We used dedicated microarrays to compare gene expression among the duodenum of Hfe(-/-) mice, induced iron overload mice, and control mice. We found 151 differentially expressed genes and unknown sequences between Hfe(-/-) mice and normal littermates. Gene profiling revealed a gene subset more specific for Hfe inactivation. The functional annotation of upregulated genes highlighted that mucus production and cell maintenance may account for the influence of Hfe on epithelium integrity and luminal iron uptake.
铁的吸收、分布、利用和储存被认为受到严格调控,因为铁储存的改变可能导致细胞损伤和疾病。遗传性血色素沉着症基因产物HFE在十二指肠隐窝中表达,但其抑制铁吸收的分子机制仍不清楚。在本研究中,我们旨在确定Hfe(-/-)小鼠十二指肠上皮细胞的转录谱。我们使用专用微阵列比较Hfe(-/-)小鼠、诱导铁过载小鼠和对照小鼠十二指肠之间的基因表达。我们发现Hfe(-/-)小鼠与正常同窝小鼠之间有151个差异表达基因和未知序列。基因谱分析揭示了一个对Hfe失活更具特异性的基因子集。上调基因的功能注释突出表明,黏液产生和细胞维持可能解释了Hfe对上皮完整性和腔内铁摄取所产生的影响。