Levin M S, Davis A E
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Nutr. 1997 Jan;127(1):13-7. doi: 10.1093/jn/127.1.13.
Cellular retinol binding protein II (CRBPII) is an abundant small intestinal protein that facilitates vitamin A trafficking and metabolism. The magnitude of retinol uptake and metabolism correlate to CRBPII levels in the human intestinal Caco-2 cell line. To investigate the importance of retinoic acid receptor response elements in the promoter of the CRBPII gene, retinoic acid regulation of CRBPII expression and vitamin A absorption was studied in differentiated Caco-2 cells. All-trans- or 9-cis-retinoic acid increased CRBPII mRNA levels two- to threefold. This was associated with a 50% increase in retinol absorption. Retinoic acid receptor beta and apolipoprotein A1 regulatory protein-1, two nuclear receptors that bind to the CRBPII promoter, were also induced, whereas other retinoid and orphan receptors were not. Thus, retinoic acid may regulate CRBPII expression directly or by selectively changing levels of nuclear receptors or other factors. These studies are the first to demonstrate that retinoic acid can modulate endogenous CRBPII mRNA levels and retinol absorption in Caco-2 cells and suggest that human intestinal vitamin A absorption may be regulated by retinoids.
细胞视黄醇结合蛋白II（CRBPII）是一种在小肠中大量存在的蛋白质，它有助于维生素A的运输和代谢。视黄醇摄取和代谢的程度与人类肠道Caco-2细胞系中的CRBPII水平相关。为了研究CRBPII基因启动子中视黄酸受体反应元件的重要性，在分化的Caco-2细胞中研究了视黄酸对CRBPII表达和维生素A吸收的调节作用。全反式或9-顺式视黄酸使CRBPII mRNA水平提高了两到三倍。这与视黄醇吸收增加50%相关。视黄酸受体β和载脂蛋白A1调节蛋白-1这两种与CRBPII启动子结合的核受体也被诱导，而其他类视黄醇和孤儿受体则没有。因此，视黄酸可能直接调节CRBPII的表达，或通过选择性改变核受体或其他因子的水平来调节。这些研究首次证明视黄酸可以调节Caco-2细胞中内源性CRBPII mRNA水平和视黄醇吸收，并表明人类肠道维生素A吸收可能受类视黄醇调节。
