Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

Sita Virakul, Judith W Heutz, Virgil A S H Dalm, Robin P Peeters, Dion Paridaens, Willem A van den Bosch, Nattiya Hirankarn, P Martin van Hagen, Willem A Dik

Research output: Contribution to journalArticleResearchpeer-review


Orbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown. We found that bFGF stimulated proliferation and hyaluronan production, but not IL-6 production by orbital fibroblasts, while VEGF hardly affected orbital fibroblast activity. Remarkably, co-stimulation of orbital fibroblasts with bFGF and PDGF-BB synergistically enhanced IL-6 and hyaluronan production and displayed an additive effect on proliferation compared to either bFGF or PDGF-BB stimulation. Nintedanib, a FGF- and PDGF-receptor targeting drug, more efficiently blocked bFGF + PDGF-BB-induced IL-6 and hyaluronan production than dasatinib that only targets PDGF-receptor. In conclusion, bFGF may contribute to orbital inflammation and tissue remodeling in GO, especially through synergistic interaction with PDGF-BB. Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO.

Original languageEnglish
Pages (from-to)94-104
Number of pages11
JournalMolecular and Cellular Endocrinology
Publication statusPublished - 15 Sept 2016


  • Adult
  • Becaplermin
  • Cell Proliferation/drug effects
  • Cells, Cultured
  • Dasatinib/pharmacology
  • Female
  • Fibroblast Growth Factors/metabolism
  • Fibroblasts/drug effects
  • Graves Ophthalmopathy/metabolism
  • Humans
  • Hyaluronic Acid/metabolism
  • Indoles/pharmacology
  • Interleukin-6/metabolism
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-sis/metabolism
  • Receptors, Platelet-Derived Growth Factor/metabolism
  • Vascular Endothelial Growth Factor A/metabolism


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