Isx Participates in the Maintenance of Vitamin A Metabolism by Regulation of β-Carotene 15,15′-Monooxygenase (Bcmo1) Expression*
Isx Participates in the Maintenance of Vitamin A Metabolism by Regulation of β-Carotene 15,15′-Monooxygenase (Bcmo1) Expression*
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DOI：
10.1074/jbc.m707928200
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发表时间：
2008-02
影响因子：
4.8
通讯作者：
Y. Seino;T. Miki;H. Kiyonari;T. Abe;Wakako Fujimoto;K. Kimura;A. Takeuchi;Yoshihisa Takahashi;Y. Oiso;T. Iwanaga;S. Seino
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文献类型：
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作者：
Y. Seino;T. Miki;H. Kiyonari;T. Abe;Wakako Fujimoto;K. Kimura;A. Takeuchi;Yoshihisa Takahashi;Y. Oiso;T. Iwanaga;S. Seino
ISX（intestinal specific homeobox）是一种肠特异性转录因子。为了阐明其生理功能，我们通过敲入Isx基因座中的β-半乳糖苷酶基因（LacZ）来产生Isx缺陷小鼠（IsxLacZ/LacZ小鼠）。对杂合子（IsxLacZ/+）小鼠的LacZ染色显示，Isx在从十二指肠到近端结肠的肠上皮细胞中大量表达。十二指肠和空肠的定量mRNA表达谱显示，β-胡萝卜素15，15 ′-单加氧酶（EC 1.14.99.36 Bcmo1）和B类I型清道夫受体（分别参与维生素A合成和类胡萝卜素摄取）在IsxLacZ/LacZ小鼠中显著增加。虽然轻度维生素A缺乏降低了野生型（Isx +/+）小鼠十二指肠的Isx表达，但严重维生素A缺乏降低了Isx +/+小鼠十二指肠和空肠的Isx mRNA表达。另一方面，维生素A缺乏增加Bcmo1在Isx +/+小鼠的十二指肠和空肠中的表达。然而，轻度维生素A缺乏并没有增加IsxLacZ/LacZ小鼠十二指肠中Bcmo1的表达。这些数据表明，Isx通过调节Bcmo1在肠道中的表达参与维生素A代谢的维持。
Isx (intestine specific homeobox) is an intestine-specific transcription factor. To elucidate its physiological function, we generated Isx-deficient mice by knocking in the β-galactosidase gene (LacZ) in the Isx locus (IsxLacZ/LacZ mice). LacZ staining of heterozygous (IsxLacZ/+) mice revealed that Isx was expressed abundantly in intestinal epithelial cells from duodenum to proximal colon. Quantitative mRNA expression profiling of duodenum and jejunum showed that β-carotene 15,15′-monooxygenase (EC1.14.99.36 Bcmo1) and the class B type I scavenger receptor, which are involved in vitamin A synthesis and carotenoid uptake, respectively, were drastically increased in IsxLacZ/LacZ mice. Although mild vitamin A deficiency decreased Isx expression in duodenum of wild-type (Isx+/+) mice, severe vitamin A deficiency decreased Isx mRNA expression in both duodenum and jejunum of Isx+/+ mice. On the other hand, vitamin A deficiency increased Bcmo1 expression in both duodenum and jejunum of Isx+/+ mice. However, Bcmo1 expression was not increased in duodenum of IsxLacZ/LacZ mice by mild vitamin A deficiency. These data suggest that Isx participates in the maintenance of vitamin A metabolism by regulating Bcmo1 expression in the intestine.