BIBF1120 inhibits proliferation and fibulin-1 production from fibroblasts

J. Burgess, L. Munk, J. Jaffar, J. Black, B. Oliver

Research output: Contribution to journalMeeting AbstractAcademic


Aim: In patients with idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, advancing fibrosis, driven by transforming growth factor-beta 1 (TGFβ1), results in excessive extracellular matrix (ECM) deposition. Our recent studies have shown that the glycoprotein fibulin-1 is increased in serum and lung tissue from patients with IPF and that their fibroblasts, which are the main effector cells for fibrosis, produce more fibulin-1 than those from healthy people. What regulates fibroblast derived fibulin-1 in people with IPF is unknown. Methods: Primary parenchymal fibroblasts were derived from five patients with IPF and five patients without IPF (Non-IPF). The production of fibulin-1 in the presence of cigarette smoke extract (CSE), foetal bovine serum (FBS) or transforming growth factor (TGF)β1 in the presence or absence of BIBF1120 (a triple kinase inhibitor) was measured by RT PCR or ELISA. Cytotoxicity of BIBF1120 was investigated by LDH-assay. Proliferation was measured by MTT and CyQuant and cell attachment was assessed by toluidine blue absorbance in fibroblasts from both groups. Results: CSE did not modulate fibulin-1 expression. Fibroblasts from IPF patients proliferated faster in 10% FBS and deposited more fibulin-1 in the presence of TGF-β1, compared to Non-IPF fibroblasts. Attachment did not differ between the fibroblast groups. BIBF1120 reduced proliferation and FBLN-1 deposition in the ECM, but did not influence attachment of fibroblasts. There were no differences in the responses between fibroblasts from patients with and without IPF. Conclusion: BIBF1120 inhibits fibroblastic processes that contribute to the pathogenesis of IPF. This new therapeutic may be effective in targeting the development of fibrosis in IPF patients.
Original languageEnglish
Pages (from-to)59
Number of pages1
Publication statusPublished - 1-Mar-2015


  • nintedanib
  • fibulin
  • glycoprotein
  • transforming growth factor beta1
  • tolonium chloride
  • transforming growth factor
  • cigarette smoke
  • phosphotransferase inhibitor
  • lactate dehydrogenase
  • society
  • fibroblast
  • Australia and New Zealand
  • Australian
  • New Zealand
  • human
  • patient
  • fibrosis
  • serum
  • fibrosing alveolitis
  • lung parenchyma
  • extracellular matrix
  • cytotoxicity
  • cell adhesion
  • effector cell
  • normal human
  • interstitial lung disease
  • assay
  • pathogenesis
  • enzyme linked immunosorbent assay

Cite this