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FK506-Binding Protein 13 Expression Is Upregulated in Interstitial Lung Disease and Correlated with Clinical Severity. A Potentially Protective Role
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 64:235-246
- Publication Year :
- 2021
- Publisher :
- American Thoracic Society, 2021.
-
Abstract
- Pulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. Endoplasmic reticulum (ER) stress initiates the unfolded protein response (UPR), a cellular stress response pathway that has been implicated in both inflammatory and fibrotic processes. Here, we sought to investigate the role of the 13 kDa FK506-binding protein (FKBP13), an ER stress-inducible molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy samples from 24 patients with idiopathic pulmonary fibrosis (IPF) and 17 control subjects. FKBP13 expression was found to be elevated in the fibrotic regions of IPF lung tissues, and within this cohort, was correlated with declining forced vital capacity and dyspnea severity. FKBP13 expression was also increased in lung biopsies of patients with hypersensitivity pneumonitis, rheumatoid arthritis, and sarcoidosis-associated interstitial lung disease. We next evaluated the role of this protein using FKBP13-/- mice in a bleomycin model of pulmonary fibrosis. Animals were assessed for lung function and histopathology at different stages of lung injury including the inflammatory (Day 7), fibrotic (Day 21) and resolution (Day 50) phase. FKBP13-/- mice showed increased infiltration of inflammatory cells and cytokines at Day 7, increased lung elastance and fibrosis at Day 21, and impaired resolution of fibrosis at Day 50. These changes were associated with an increased number of cells that stained positive for TUNEL and cleaved caspase 3 in the FKBP13-/- lungs, indicating a heightened cellular sensitivity to bleomycin. Our findings suggest that FKBP13 is a potential biomarker for severity or progression of interstitial lung diseases, and that it has a biologically relevant role in protecting mice against bleomycin-induced injury, inflammation and fibrosis.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Clinical Biochemistry
Inflammation
Lung injury
Bleomycin
Extracellular matrix
Idiopathic pulmonary fibrosis
chemistry.chemical_compound
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Fibrosis
Pulmonary fibrosis
medicine
Molecular Biology
030304 developmental biology
0303 health sciences
Lung
business.industry
Interstitial lung disease
Cell Biology
respiratory system
medicine.disease
respiratory tract diseases
3. Good health
medicine.anatomical_structure
030104 developmental biology
FKBP
chemistry
030228 respiratory system
Cancer research
Unfolded protein response
medicine.symptom
business
Myofibroblast
Hypersensitivity pneumonitis
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....813e63ee9e89068286356ebacfc0eb8a