SFTA2—A Novel Secretory Peptide Highly Expressed in the Lung—Is Modulated by Lipopolysaccharide but Not Hyperoxia

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.

“SP-G”, a Putative New Surfactant Protein – Tissue Localization and 3D Structure

“…For testing the antibodies, we performed Western blot analysis using human lung tissue, because all known surfactant proteins were identified and characterized also in the lung [1], [2], [13], [64], [65]. Furthermore, a very recent study of Mittal et al also demonstrated the presence of SP-G within lung tissue [66]. The corresponding Western blot analysis show specific bands at 11 kDa, 20 kDa and 30 kDa.…”

Methodological approach from the Best Overall Team in the sbv IMPROVER Diagnostic Signature Challenge

“…28 Remarkably, three small prolinerich protein encoding genes (SPRR1A, SPRR1B, and SPRR3) and four surfactant or surfactant-associated protein encoding genes (SFTPA2, SFTPB, SFTA2, and SFTA3) were also on our selected list, in accordance with the former trio being highly expressed in squamous epithelial cells and carcinomas, 29 and the latter being characteristic for secretory alveolar cells and ACs. [30][31][32] Another gene from our list, DSG3, encodes for desmoglein 3, a component of the intercellular desmosomal junction, which is highly upregulated in squamous cell carcinoma of the lung, compared with AC, and has been suggested as a good marker of the former. 33,34 The strengths of our approach reside in the fact that it proved to be reliable on several data sets with relatively minimal user interaction in the process and tuning from one data set to the other.…”

Pneumonia: host susceptibility and shared genetics with pulmonary function and other traits

“…SFTA2 orthologs are present in all mammals. In a mouse model, Sfta2 was strongly down‐regulated after intratracheal injections of lipopolysaccharides ; it was also found to be implicated in lung function development . SFTA2 SNPs were associated with four of six PF phenotypes under study available through the Global Biobank Engine.…”

“…SFTA2 (SP‐G) protein is highly expressed in lung; namely, in alveolar type II and in non‐ciliated bronchiolar cells. It is expressed in parallel with hydrophobic surfactant proteins B and C, and has physicochemical properties similar to those known for these surfactants . SFTA2 orthologs are present in all mammals.…”

“…As a result, the proinflammatory background is maintained and facilitates the development of infection. Taking into account a possible regulatory role of SFTA2 in inflammation and defense , SFTA2 down‐regulation and VARS2 up‐regulation in the same individuals may further increase the risk of pneumonia.…”