Molecular cloning and characterization of spurt, a human novel gene that is retinoic acid-inducible and encodes a secretory protein specific in upper respiratory tracts

Abstract

Retinoids, such as all-trans-retinoic acid, play an essential role in the regulation of airway epithelial cell growth, differentiation, and gene expression. Using cDNA microarray, we identified a clone, DD4, that contains the cDNA of a novel gene, spurt (secretory protein in upper respiratory tracts) that was significantly induced by all-trans-retinoic acid in primary cultured human tracheobroncheal epithelia. Two alternatively spliced spurt transcripts of 1090 and 1035 base pairs exist that contain the same open reading frame expressing a 256-amino acid peptide. The full-length spurt cDNA sequence spans a genomic DNA fragment of 7,313 bp, and the gene is located on chromosome 20q11.21. spurt mRNA is notably expressed at high levels in human nasal, tracheal, and lung tissues. In situ hybridization demonstrated that spurt message is often present in secretory cell types. The human spurt gene product is a secretory protein that contains a distinct signal peptide sequence in its first 19 amino acids. Mono-specific antibodies were generated to characterize spurt expression. Our data demonstrate that spurt is secreted onto the apical side of primary human airway epithelial cultures and is present in clinical sputum samples. spurt gene expression is higher in sputum and tissue samples obtained from patients with chronic obstructive lung disease. Our results provide the cloning and characterization of this tissue-specific novel gene and its possible relationship with airway diseases.