Bhat P V, Bader T, Nettesheim P, Jetten A M
CHUM Research Centre, Hôtel-Dieu Pavilion, Department of Medicine, University of Montreal, QC, Canada.
Biochem Cell Biol. 1998;76(1):59-62.
Retinoic acid (RA), a metabolite of vitamin A, is known to be a key signaling molecule in regulating epithelial cell differentiation. We recently characterized and cloned a retinal dehydrogenase (RALDH) that catalyzes the oxidation of retinal to RA. In this study, we investigated the effects of retinoids on the level of RALDH mRNA and protein as well as RALDH activity in the trachea and cultured tracheal epithelial cells. Vitamin A deficiency induced squamous metaplasia in the tracheal epithelium and down-regulated RALDH expression. Supplementation of retinol and retinoic acid to vitamin A deficient rats restored the normal mucociliary epithelium and up-regulated the RALDH expression. In rat epithelial cells cultured in vitro, RAinhibited squamous differentiation and promoted mucociliary differentiation. Squamous differentiated cultures (RA-) expressed very low levels of RALDH mRNA, whereas mucociliary differentiated cultures (RA+) expressed high levels of RALDH mRNA. Retinal and retinol were poor inducers of mucociliary differentiation as well as RALDH expression. The RALDH expression paralleled the expression of the mucin-1 gene in mucociliary cultures. These results suggest that the expression of RALDH is dependent on the differentiation state of the airway epithelium.
视黄酸（RA）是维生素A的一种代谢产物，已知是调节上皮细胞分化的关键信号分子。我们最近鉴定并克隆了一种视网膜脱氢酶（RALDH），它催化视网膜氧化为RA。在本研究中，我们研究了类维生素A对气管和培养的气管上皮细胞中RALDH mRNA和蛋白水平以及RALDH活性的影响。维生素A缺乏诱导气管上皮鳞状化生并下调RALDH表达。给维生素A缺乏的大鼠补充视黄醇和视黄酸可恢复正常的黏液纤毛上皮并上调RALDH表达。在体外培养的大鼠上皮细胞中，RA抑制鳞状分化并促进黏液纤毛分化。鳞状分化培养物（RA-）中RALDH mRNA表达水平极低，而黏液纤毛分化培养物（RA+）中RALDH mRNA表达水平高。视网膜和视黄醇对黏液纤毛分化以及RALDH表达的诱导作用较弱。在黏液纤毛培养物中，RALDH表达与黏蛋白-1基因的表达平行。这些结果表明，RALDH的表达取决于气道上皮的分化状态。
