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SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis.
- Source :
-
JCI insight [JCI Insight] 2024 Jun 10; Vol. 9 (11). Date of Electronic Publication: 2024 Jun 10. - Publication Year :
- 2024
-
Abstract
- Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.
- Subjects :
- Humans
Animals
Mice
Male
Female
Middle Aged
Aged
Lung Diseases, Interstitial blood
Lung Diseases, Interstitial diagnosis
Lung Diseases, Interstitial pathology
Lung Diseases, Interstitial metabolism
Lung pathology
Lung metabolism
Proteomics methods
Disease Models, Animal
Prognosis
Protein Precursors
Pulmonary Surfactant-Associated Proteins
Extracellular Vesicles metabolism
Biomarkers blood
Pulmonary Fibrosis blood
Pulmonary Fibrosis metabolism
Pulmonary Fibrosis pathology
Disease Progression
Pulmonary Surfactant-Associated Protein B blood
Pulmonary Surfactant-Associated Protein B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 38855869
- Full Text :
- https://doi.org/10.1172/jci.insight.177937