Sodium butyrate stimulates NHE8 expression via its role on activating NHE8 basal promoter activity.
Sodium butyrate stimulates NHE8 expression via its role on activating NHE8 basal promoter activity.
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DOI：
10.1152/ajpgi.00194.2015
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Hua Xu;A. McCoy;Jing Li;Yang Zhao;F. Ghishan
中科院分区：
文献类型：
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作者：
Hua Xu;A. McCoy;Jing Li;Yang Zhao;F. Ghishan
丁酸盐是结肠腔内的主要代谢物。它是由细菌发酵的膳食纤维生产的。丁酸盐通过调节钠/氢交换器3(NHE3)刺激电子中性钠的吸收。尽管NHE8是肠道NHE家族的最新成员，参与了肠道对钠的吸收，但丁酸是否调节NHE8在肠道上皮细胞中的表达尚不清楚。在目前的研究中，我们发现丁酸处理强烈地诱导了人肠上皮细胞NHE8蛋白和NHE8mRNA的表达。用人NHE8启动子报告载体转染细胞，结果表明，丁酸处理可刺激报告基因的表达，其刺激程度与其对NHE8基因表达的刺激程度相当。有趣的是，在曲古菌素(TSA)处理后的人NHE8启动子转基因细胞中也观察到了类似的结果。凝胶迁移率改变分析发现，在丁酸刺激下，SP3蛋白与人NHE8基本启动子区域的结合增强。此外，SP3乙酰化修饰参与了丁酸介导的Caco-2细胞中NHE8的激活。我们的发现表明，丁酸对NHE8基因表达的作用机制涉及增强人NHE8基因启动子碱基启动子区域的SP3相互作用，以激活NHE8基因转录。因此，丁酸盐参与了NHE8的肠道调节，从而促进了钠的吸收。
Butyrate is a major metabolite in colonic lumen. It is produced from bacterial fermentation of dietary fiber. Butyrate has been shown to stimulate electroneutral sodium absorption through its regulation on sodium/hydrogen exchanger 3 (NHE3). Although NHE8, the newest addition of intestinal NHE family, is involved in sodium absorption in the intestinal tract, whether butyrate modulates NHE8 expression in the intestinal epithelial cells is not known. In the current study, we showed that butyrate treatment strongly induced NHE8 protein and NHE8 mRNA expression in human intestinal epithelial cells. Transfection with the human NHE8 promoter reporter constructs showed that butyrate treatment stimulated reporter gene expression at an amount comparable with its stimulation of NHE8 mRNA expression. Interestingly, a similar result was also observed in human NHE8 promoter transfected cells after trichostatin (TSA) treatment. Gel mobility shift assay identified an enhanced Sp3 protein binding on the human NHE8 basal promoter region upon butyrate stimulation. Furthermore, Sp3 acetylation modification is involved in butyrate-mediated NHE8 activation in Caco-2 cells. Our findings suggest that the mechanism of butyrate action on NHE8 expression involves enhanced Sp3 interaction at the basal promoter region of the human NHE8 gene promoter to activate NHE8 gene transcription. Thus butyrate is involved in intestinal regulation of NHE8 resulting enhanced sodium absorption.