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小鼠十二指肠上皮中与HFE和铁状态相关基因的差异表达。

Differential expression of genes related to HFE and iron status in mouse duodenal epithelium.

作者信息

Abgueguen Emmanuelle, Toutain Bertrand, Bédrine Hélène, Chicault Céline, Orhant Magali, Aubry Marc, Monnier Annabelle, Mottier Stéphanie, Jouan Hélène, Bahram Seiamak, Mosser Jean, Fergelot Patricia

机构信息

CNRS UMR 6061, Université de Rennes1, IFR 140, Faculté de Médecine, CS 34317, 35043 Rennes, France.

出版信息

Mamm Genome. 2006 May;17(5):430-50. doi: 10.1007/s00335-005-0122-z.

DOI:10.1007/s00335-005-0122-z
PMID:16688533
Abstract

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.

摘要

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。

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Differential expression of genes related to HFE and iron status in mouse duodenal epithelium.小鼠十二指肠上皮中与HFE和铁状态相关基因的差异表达。
Mamm Genome. 2006 May;17(5):430-50. doi: 10.1007/s00335-005-0122-z.
2
Gene expression profiling of Hfe-/- liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers.对铁负荷易感性不同的小鼠品系中Hfe基因敲除肝脏和十二指肠进行基因表达谱分析:鉴定Hfe的转录调控靶点及潜在的血色素沉着症修饰因子。
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Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis.肝脏和肠道中的调节缺陷表明小鼠血色素沉着症中存在异常的铁调素和Cybrd1表达。
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引用本文的文献

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Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.肝铁调节蛋白缺乏和膳食铁过载对小鼠肝脏和十二指肠的全球转录反应。
PLoS One. 2009 Sep 29;4(9):e7212. doi: 10.1371/journal.pone.0007212.
2
Small proline-rich proteins (SPRR) function as SH3 domain ligands, increase resistance to injury and are associated with epithelial-mesenchymal transition (EMT) in cholangiocytes.富含脯氨酸的小分子蛋白(SPRR)作为SH3结构域配体发挥作用,增强对损伤的抵抗力,并与胆管细胞的上皮-间质转化(EMT)相关。
J Hepatol. 2008 Feb;48(2):276-88. doi: 10.1016/j.jhep.2007.09.019. Epub 2007 Dec 17.

本文引用的文献

1
Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis.基因表达谱显示,在石棉诱导的纤维化小鼠模型中,mClca3(Gob5)表达增加且粘蛋白生成增多。
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Blue native/SDS-PAGE analysis reveals reduced expression of the mClCA3 protein in cystic fibrosis knock-out mice.蓝色天然/SDS-聚丙烯酰胺凝胶电泳分析显示,囊性纤维化基因敲除小鼠中mClCA3蛋白的表达降低。
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Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma.
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Orchestration of iron homeostasis.铁稳态的调控
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Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function.人体中的铁调素水平与肝脏铁储备、血红蛋白水平及肝功能相关。
Blood. 2005 Jul 15;106(2):746-8. doi: 10.1182/blood-2004-12-4855. Epub 2005 Mar 29.
6
Expression and regulation of small proline-rich protein 2 in allergic inflammation.富含脯氨酸的小分子蛋白2在变应性炎症中的表达与调控
Am J Respir Cell Mol Biol. 2005 May;32(5):428-35. doi: 10.1165/rcmb.2004-0269OC. Epub 2005 Feb 24.
7
Small proline-rich proteins 2 are noncoordinately upregulated by IL-6/STAT3 signaling after bile duct ligation.富含脯氨酸的小分子蛋白2在胆管结扎后被白细胞介素-6/信号转导和转录激活因子3信号通路非协调性上调。
Lab Invest. 2005 Jan;85(1):109-23. doi: 10.1038/labinvest.3700213.
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Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.铁调素通过与铁转运蛋白结合并诱导其内化来调节细胞铁外流。
Science. 2004 Dec 17;306(5704):2090-3. doi: 10.1126/science.1104742. Epub 2004 Oct 28.
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Respiratory syncytial virus in allergic lung inflammation increases Muc5ac and gob-5.过敏性肺部炎症中的呼吸道合胞病毒会增加Muc5ac和gob-5的表达。
Am J Respir Crit Care Med. 2004 Aug 1;170(3):306-12. doi: 10.1164/rccm.200301-030OC. Epub 2004 May 6.
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Genomics. 2004 May;83(5):772-89. doi: 10.1016/j.ygeno.2003.11.014.