Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/7315
Title: Idiopathic Pulmonary Fibrosis Serum proteomic analysis before and after nintedanib therapy
Authors: Landi, Claudia
Bergantini, Laura
Cameli, Paolo
d'Alessandro, Miriana
Carleo, Alfonso
Shaba, Enxhi
Rottoli, Paola
Bini, Luca
Bargagli, Elena
Issue Date: 2020
Project: None 
Journal: SCIENTIFIC REPORTS
Abstract: 
Idiopathic pulmonary fibrosis (IPF) is a fatal progressive disease with a median survival of 2-5 years. Nintedanib is a small tyrosine kinase inhibitor that reduces IPF progression, significantly slowing the annual decline in Forced Vital Capacity (FVC). Very little data is available on the molecular mechanisms of this treatment in IPF, despite a growing interest in the definition of IPF pathogenesis and target therapy. A functional proteomic approach was applied to the analysis of serum samples from IPF patients in order to highlight differential proteins potentially indicative of drug-induced molecular pathways modifications and response to therapy. Twelve serum samples were collected from six IPF patients in care at Siena Regional Referral Center for Interstitial Lung Diseases (ILDs) and treated with nintedanib for one year. Serum samples were analyzed at baseline (T0 before starting therapy) and after one year of treatment (T1) and underwent differential proteomic and bioinformatic analysis. Proteomic analysis revealed 13 protein species that were significantly increased after one year of treatment. When the targets of nintedanib (VEGFR, FGFR and PDGFR) were added, enrichment analysis extracted molecular pathways and process networks involved in cell differentiation (haptoglobin and albumin), coagulation (antithrombin III), epithelial mesenchymal transition, cell proliferation and transmigration. PI3K and MAPK induced up-regulation of apolipoprotein C3. Proteomic study found 13 protein species up-regulated in IPF patients after one year of nintedanib treatment. Haptoglobin, a central hub of our analysis was validated by 2D-WB and ELISA as theranostic marker in a more numerous populations of patients.
Description: 
213798
URI: http://hdl.handle.net/20.500.12779/7315
ISSN: 2045-2322
DOI: 10.1038/s41598-020-66296-z
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