Characterization of a novel airway epithelial cell specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol

Multiple retinoic acid responsive cDNAs were isolated from a high density c DNA microarray membrane, which was developed from a cDNA Library of human t racheobronchial epithelial cells. Five selected cDNA clones encoded the seq uence of the same novel gene. The predicted open reading frame of the novel gene encoded a protein of 319 amino acids. The deduced amino acid sequence contains four motifs that are conserved in the short-chain alcohol dehydro genase/reductase (SDR) family of proteins. The novel gene shows the greates t homology to a group of dehydrogenases that can oxidize retinol (retinol d ehydrogenases), The mRNA of the novel gene was found in trachea, colon, ton gue, and esophagus. In situ hybridization of airway tissue sections demonst rated epithelial cell-specific gene expression, especially in the ciliated cell type. Both all-trans-retinoic acid and g-cis-retinoic acid were able t o elevate the expression of the novel gene in primary human tracheobronchia l epithelial cells in vitro. This elevation coincided with an enhanced reti nol metabolism in these cultures. COS cells transfected with an expression construct of the novel gene were also elevated in the metabolism of retinol . The results suggested that the novel gene represents a new member of the SDR family that may play a critical role in retinol metabolism in airway ep ithelia as well as in other epithelia of colon, tongue, and esophagus.