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

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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.