Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum
Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum
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DOI：
10.1152/ajpgi.00489.2004
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发表时间：
2005-05-01
影响因子：
4.5
通讯作者：
Ghishan, FK
中科院分区：
文献类型：
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作者：
Collins, JF;Franck, CA;Ghishan, FK
我们试图通过诱导大鼠从哺乳期到成年期的出生后发育过程中的铁缺乏来确定参与肠道铁吸收的新基因。然后，我们用来自十二指肠粘膜的cRNA进行比较基因芯片分析（RAE 230 A和RAE 230 B芯片; Affytron）。实时PCR用于确认基因表达的变化。编码顶端铁转运相关蛋白[二价金属转运蛋白1（DMT 1）和十二指肠细胞色素B]的基因在所有年龄段的研究强烈诱导，而增加的mRNA编码的基底侧蛋白铁调节基因1和hephaestin只观察到实时PCR。此外，转铁蛋白受体1和血红素加氧酶1被诱导。我们还发现了以前与肠道铁转运无关的新基因的诱导。门克斯铜ATP酶（ATP 7a）和金属硫蛋白强烈诱导在所有年龄段的研究，表明增加铜的吸收肠细胞缺铁。我们还发现，7至12周龄缺铁大鼠的肝脏铜水平显着增加。在大多数年龄段，钠依赖性维生素C转运蛋白、三重基序蛋白27、水通道蛋白4、脂质运载蛋白相互作用膜受体和乳腺癌耐药蛋白（ABCG 2）也上调。一些基因的表达也随着铁剥夺而下降，包括几种膜转运蛋白、代谢酶和参与氧化应激反应的基因。我们推测，膳食铁剥夺导致增加肠道铜的吸收，通过DMT 1的刷状缘膜和门克斯铜ATP酶的基底外侧膜。因此，这些发现可以解释在缺铁状态下的铜负载。我们还表明，许多其他新的基因可能是差异调节设置铁剥夺。
We sought to identify novel genes involved in intestinal iron absorption by inducing iron deficiency in rats during postnatal development from the suckling period through adulthood. We then performed comparative gene chip analyses (RAE230A and RAE230B chips; Affymetrix) with cRNA derived from duodenal mucosa. Real-time PCR was used to confirm changes in gene expression. Genes encoding the apical iron transport-related proteins [divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR. In addition, transferrin receptor 1 and heme oxygenase 1 were induced. We also identified induction of novel genes not previously associated with intestinal iron transport. The Menkes copper ATPase (ATP7a) and metallothionein were strongly induced at all ages studied, suggesting increased copper absorption by enterocytes during iron deficiency. We also found significantly increased liver copper levels in 7- to 12-wk-old iron-deficient rats. Also upregulated at most ages examined were the sodium-dependent vitamin C transporter, tripartite motif protein 27, aquaporin 4, lipocalin-interacting membrane receptor, and the breast cancer-resistance protein (ABCG2). Some genes also showed decreased expression with iron deprivation, including several membrane transporters, metabolic enzymes, and genes involved in the oxidative stress response. We speculate that dietary iron deprivation leads to increased intestinal copper absorption via DMT1 on the brush-border membrane and the Menkes copper ATPase on the basolateral membrane. These findings may thus explain copper loading in the iron-deficient state. We also demonstrate that many other novel genes may be differentially regulated in the setting of iron deprivation.