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LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis
- Source :
- Clinical Science (London, England : 1979)
- Publication Year :
- 2018
- Publisher :
- Portland Press Ltd., 2018.
-
Abstract
- Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage (CD45, TER-119, CD324, CD31, LYVE-1, and CD146)-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Amongst several genes up-regulated in the FACS-sorted myofibroblasts, we focussed on Ltbp2, the gene encoding latent transforming growth factor-β (TGF-β) binding protein-2 (LTBP2), because of the signal similarity to Acta2, which encodes αSMA, in the clustering analysis. The up-regulation was reproduced at the mRNA and protein levels in human lung myofibroblasts induced by TGF-β1. LTBP2 staining in IPF lungs was broadly positive in the fibrotic interstitium, mainly as an extracellular matrix (ECM) protein; however, some of the αSMA-positive myofibroblasts were also stained. Serum LTBP2 concentrations, evaluated using ELISA, in IPF patients were significantly higher than those in healthy volunteers (mean: 21.4 compared with 12.4 ng/ml) and showed a negative correlation with % predicted forced vital capacity (r = −0.369). The Cox hazard model demonstrated that serum LTBP2 could predict the prognosis of IPF patients (hazard ratio for death by respiratory events: 1.040, 95% confidence interval: 1.026–1.054), which was validated using the bootstrap method with 1000-fold replication. LTBP2 is a potential prognostic blood biomarker that may reflect the level of differentiation of lung fibroblasts into myofibroblasts in IPF.
- Subjects :
- Male
0301 basic medicine
CD31
Pathology
medicine.medical_specialty
Idiopathic pulmonary fibrosis
Microarray
Transforming Growth Factor beta1
Extracellular matrix
Bleomycin
03 medical and health sciences
medicine
Animals
Humans
Myofibroblasts
Lung
Cells, Cultured
Research Articles
Aged
Myofibroblast
biology
business.industry
Gene Expression Profiling
Biomarker
General Medicine
Fibroblasts
Middle Aged
respiratory system
medicine.disease
respiratory tract diseases
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Latent TGF-beta Binding Proteins
LTBP2
biology.protein
Biomarker (medicine)
CD146
Female
ACTA2
business
Biomarkers
Research Article
Transforming growth factor
Subjects
Details
- ISSN :
- 14708736 and 01435221
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Clinical Science
- Accession number :
- edsair.doi.dedup.....bf4b9ceb4ceadb14c245c2e7b9071d41