HNF-1α participates in glucose regulation of sucrase-isomaltase gene expression in epithelial intestinal cells
HNF-1α participates in glucose regulation of sucrase-isomaltase gene expression in epithelial intestinal cells
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DOI：
10.1016/j.bbrc.2006.12.065
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发表时间：
2007-02-16
影响因子：
3.1
通讯作者：
Tsuda, Kinsuke
中科院分区：
文献类型：
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作者：
Gu, Ning;Adachi, Tetsuya;Tsuda, Kinsuke
蔗糖-异麦芽糖酶（Sucrase-isomaltase， SI）基因的表达受葡萄糖的负调控，但其分子机制尚不完全清楚。本研究的目的是探讨HNF-1 α和HNF-1 β是否参与葡萄糖对SI基因表达的调节。为了探讨这个问题，我们在含有2.0和16.7 mM葡萄糖的培养基中培养Caco-2细胞，研究了SI与HNF-1 α和HNF-1 β之间的基因表达关系。我们发现HNF-1 α的基因表达与葡萄糖调节的SI呈正相关，而非HNF-1 β。此外，为了阐明当HNF-1 α和HNF-1 β被抑制时，葡萄糖对SI基因表达的调节是否会改变，我们制作了三个稳定的细胞系，分别稳定表达显性阴性突变体HNF-1 α T539fsdelC、突变体HNF-1 β R177X和空载体（作为对照）。我们发现葡萄糖对SI基因表达的调节在HNF-1 α T539fsdelC细胞中显著减弱，但在空载体和HNF-1 β R177X细胞中维持良好。这些结果表明，HNF-1 α参与了葡萄糖对SI基因表达的调控。(c) 2006爱思唯尔公司版权所有。
Sucrase-isomaltase (SI) gene expression is negatively regulated by glucose, but its molecular mechanism is not completely clear. The purpose of this study is to investigate whether HNF-1 alpha and HNF-1 beta contribute to glucose regulation of SI gene expression. To explore this question, we examined the association of gene expressions between SI and HNF-1 alpha and HNF-1 beta in Caco-2 cells cultured in medium containing 2.0 and 16.7 mM glucose. We found that gene expression of HNF-1 alpha but not HNF-1 beta exhibits a positive correlation with that of SI regulated by glucose. Moreover, to elucidate whether glucose regulation of SI gene expression is changed when HNF-1 alpha and HNF-1 beta are inhibited, we produced three stable cell lines, in which dominant-negative mutant HNF-1 alpha T539fsdelC, mutant HNF-1 beta R177X, and empty vector (as a control), respectively, were stably expressed. We found that the glucose regulation of SI gene expression was significantly attenuated in HNF-1 alpha T539fsdelC cells, but it was well maintained in empty vector and HNF-1 beta R177X cells. These results suggest that HNF-1 alpha participates in glucose regulation of SI gene expression. (c) 2006 Elsevier Inc. All rights reserved.