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Open Access 01-12-2014 | Research

Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis

Authors: Katrin E Hostettler, Jun Zhong, Eleni Papakonstantinou, George Karakiulakis, Michael Tamm, Petra Seidel, Qingzhu Sun, Jyotshna Mandal, Didier Lardinois, Christopher Lambers, Michael Roth

Published in: Respiratory Research | Issue 1/2014

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.

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Title: Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis
Authors: Katrin E Hostettler
Jun Zhong
Eleni Papakonstantinou
George Karakiulakis
Michael Tamm
Petra Seidel
Qingzhu Sun
Jyotshna Mandal
Didier Lardinois
Christopher Lambers
Michael Roth
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-014-0157-3

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Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis

Abstract

Background

Aim

Results

Conclusion

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