Abstract:
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The kinase inhibitor nintedanib specific for vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR) significantly reduced the rate of decline of forced vital capacity versus placebo. AIM:To determine the in vitro effect of nintedanib on primary human lung fibroblasts. METHODS:Fibroblasts were isolated from lungs of IPF patients and from non-fibrotic controls. We assessed the effect of VEGF, PDGF-BB and basic FGF (bFGF) ± nintedanib on: (i) expression/activation of VEGFR, PDGFR, and FGFR, (ii) cell proliferation, secretion of (iii) matrix metalloproteinases (MMP), (iv) tissue inhibitor of metalloproteinase (TIMP), and (v) collagen. RESULTS:IPF fibroblasts expressed higher levels of PDGFR and FGFR than controls. PDGF-BB, bFGF, and VEGF caused a pro-proliferative effect which was prevented by nintedanib. Nintedanib enhanced the expression of pro-MMP-2, and inhibited the expression of TIMP-2. Transforming growth factor-beta-induced secretion of collagens was inhibited by nintedanib. CONCLUSION:Our data demonstrate a significant anti-fibrotic effect of nintedanib in IPF fibroblasts. This effect consists of the drug's anti-proliferative capacity, and on its effect on the extracellular matrix, the degradation of which seems to be enhanced.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Hostettler KE,Zhong J,Papakonstantinou E,Karakiulakis G,Tamm M,Seidel P,Sun Q,Mandal J,Lardinois D,Lambers C,Roth Mdoi
10.1186/s12931-014-0157-3subject
Has Abstractpub_date
2014-12-12 00:00:00pages
157eissn
1465-9921issn
1465-993Xpii
s12931-014-0157-3journal_volume
15pub_type
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abstract:: ...
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