Abstract
Tissue-specific transcripts are likely to be of importance for the corresponding organ. While attempting to define the specific transcriptome of the human lung, we identified the transcript of a yet uncharacterized protein, SFTA2. In silico analyses, biochemical methods, fluorescence imaging and animal challenge experiments were employed to characterize SFTA2. Human SFTA2 is located on Chr. 6p21.33, a disease-susceptibility locus for diffuse panbronchiolitis. RT-PCR verified the abundance of SFTA2-specific transcripts in human and mouse lung. SFTA2 is synthesized as a hydrophilic precursor releasing a 59 amino acid mature peptide after cleavage of an N-terminal secretory signal. SFTA2 has no recognizable homology to other proteins while orthologues are present in all mammals. SFTA2 is a glycosylated protein and specifically expressed in nonciliated bronchiolar epithelium and type II pneumocytes. In accordance with other hydrophilic surfactant proteins, SFTA2 did not colocalize with lamellar bodies but colocalized with golgin97 and clathrin-labelled vesicles, suggesting a classical secretory pathway for its expression and secretion. In the mouse lung, Sfta2 was significantly downregulated after induction of an inflammatory reaction by intratracheal lipopolysaccharides paralleling surfactant proteins B and C but not D. Hyperoxia, however, did not alter SFTA2 mRNA levels. We have characterized SFTA2 and present it as a novel unique secretory peptide highly expressed in the lung.
Highlights
A number of lung diseases are likely to be caused by genetic defects but their pathogenesis is not yet understood
Gene Characteristics of Human SFTA2 SFTA2 is a single copy gene on chromosome 6 p21.33. It contains 3 exons with small introns such that the total genomic region corresponding to the transcript comprises only 826 bp. This region has been associated with diffuse panbronchiolitis (DPB) in Japanese patients [11]
SFTA2 is positioned close to DPCR1, an unconfirmed candidate gene for DPB, MUC21, which encodes a mucin highly expressed in the lung, and PBMUCL1, polymorphisms of which have been associated with DPB [12]
Summary
A number of lung diseases are likely to be caused by genetic defects but their pathogenesis is not yet understood. In order to identify human genes predominantly expressed in the lung, we screened public databases containing tissue expression profiles. We identified SFTA2 as a gene expressed in the lung. The official gene symbol is SFTA2 (‘Surfactant associated 29; HUGO Nomenclature Committee; [1]). There is no published report focusing on SFTA2, Clark et al [2] predicted secretion signals for over 1000 proteins from public databases, SFTA2 being among them. Zhang and Henzel [3] tested the ability of a computer algorithm to predict cleavage sites of secretory signals in 270 secreted proteins. As yet there are no published data on expression or function of SFTA2. We present the identification of SFTA2 as a gene preferentially expressed in the lung as well as detailed expression, biochemical and regulation data
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