International journal of molecular sciences, 2021-12, Vol.22 (24), p.13421
2021
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- Autor(en) / Beteiligte
- Titel
- Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis
- Ist Teil von
- International journal of molecular sciences, 2021-12, Vol.22 (24), p.13421
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model's applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms222413421Titel-ID: cdi_doaj_primary_oai_doaj_org_article_521ce8713fc84d399ea172a287643fd3
- Format
- –
- Schlagworte
- Aged, Basic Medicine, Biomarkers, Biomarkers - metabolism, Biomechanics, CCL19 protein, Cell and Molecular Biology, Cell- och molekylärbiologi, Cellular Microenvironment - physiology, Chemokine CCL7 - metabolism, Chemokine CXCL13 - metabolism, Chemokines, Chemotaxis, Clinical Medicine, CXCL13 protein, Cytokines, Extracellular matrix, Female, Fibroblast, Fibroblasts, Fibroblasts - metabolism, Fibrosis, Gene expression, Growth factors, Humans, Idiopathic pulmonary fibrosis, Idiopathic Pulmonary Fibrosis - metabolism, Inflammation, Interleukin 6, Interleukin-6 - metabolism, Klinisk medicin, Lung - metabolism, Lung diseases, Lungmedicin och allergi, Male, Matrilysin, Matrix Metalloproteinase 7 - metabolism, Medical and Health Sciences, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Microenvironments, Middle Aged, Patients, Protein expression, Proteins, Proteomics, Proteomics - methods, Pulmonary fibrosis, Respiratory Medicine and Allergy, Serum proteins, TWEAK Receptor - metabolism, Vascular Endothelial Growth Factor A - metabolism