[HTML][HTML] Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis
KE Hostettler, J Zhong, E Papakonstantinou… - Respiratory …, 2014 - Springer
KE Hostettler, J Zhong, E Papakonstantinou, G Karakiulakis, M Tamm, P Seidel, Q Sun…
Respiratory research, 2014•SpringerBackground 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 …
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 …
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.
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