Regulation of intestinal expression of proton-coupled folate transporter and its relevance to folate malabsorption in alcohol consumption.

长期饮酒被怀疑通过降低小肠中叶酸转运蛋白的功能而导致叶酸吸收不良。因此，我们研究了乙醇和几种黄酮类化合物对质子偶联叶酸转运体（PCFT）功能的影响。用葡萄酒中的杨梅素预处理Caco-2细胞，可抑制PCFT介导的叶酸摄取，但不抑制乙醇。我们还检测了人类PCFT启动子与几种转录因子的活性，以阐明肠道PCFT表达的转录调控机制。我们发现KLF4是参与PCFT启动子激活的主要核因子，KLF4诱导的激活可能受到HNF4α、CDX2和C/EBPα的协同调节。

Chronic alcohol consumption have been suspected to cause malabsorption of folates by decreaseing the function of folate transporter(s) in small intestine. Therefore, we examined the effects of ethanol and several flavonoids on the function of proton-coupled folate transporter (PCFT). Pretreatment of Caco-2 cells with myricetin, which is included in wines, caused inhibition of the uptake of folate mediated by PCFT, but not with ethanol. We also examined human PCFT promoter activity with several transcriptional factors to elucidate transcriptional regulation mechanism involved in intestinal PCFT expression. It was found that KLF4 is a major nuclear factor involved in the activation of PCFT promoter, and the KLF4-induced activation is likely to be synergistically regulated by HNF4α, CDX2 and C/EBPα.