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.

Lung Epithelial Healing: A Modified Seed and Soil Concept

“…However, tracheal Clara-like cells express less CCSP and Cyp2F2 than bronchiolar Clara cells and have a distinct ultrastructure. Claralike cells also have a distinct secretory protein repertoire: they express high levels of the CCSP-related protein Scgb3A1 (23) and the antibacterial protein PLUNC (also termed SPURT) (24,25). In recognition of the differences between nonmucus secretory cells of the cartilaginous and bronchiolar airways, we refer to tracheal secretory cells as Clara-like cells.…”

Four Reasons to Consider a Novel Class of Innate Immune Molecules in the Oral Epithelium

“…Another common aspect of genetic structure is that the PLUNC (H) (Bingle and Bingle, 2000) LUNX (H) (Iwao et al, 2001) SPURT (H) (Di et al, 2003) Homologues (C) (Wheeler et al, 2003) (M) (Weston et al, 1999) (R) (Sung et al, 2002) (Wheeler et al, 2002) a Most of the genes in the cluster are poorly characterized and are found as database entries derived from genomic sequences, expressed sequence tags (ESTs), or predicted proteins. The gene names at the top of each column are derived from a recent survey of PLUNC genes in humans (Bingle and Craven, 2002).…”

“…"Long" PLUNC genes (LPUNC-1, 2, 3, and 4) have 15 or 16 exons and encode proteins approximately 480 amino acids long. Several groups have reported alternative splice variants that omit one or more exons (e.g., Di et al, 2003).…”

“…are predicted to appear in humans Craven, 2002, 2003;Di et al, 2003), and multiple homologues have been identified in rats and cows (Sung et al, 2002;Wheeler et al, 2002;Ball et al, 2003). Although their names and functions are obscure, these molecules are united by four areas of evidence that suggest a common ancestry and role in innate immunity:…”

Increased expression of BPI fold-containing family A member 1 is associated with metastasis and poor prognosis in human colorectal carcinoma

“…A number of previous studies have demonstrated that BPIFA1 is involved in various physiological and pathological processes (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). It is considered to be involved in inflammatory responses to irritants in the upper airway (2-7).…”