Mutant soluble ectodomain of fibroblast growth factor receptor-2 IIIc attenuates bleomycin-induced pulmonary fibrosis in mice

Biol Pharm Bull. 2012;35(5):731-6. doi: 10.1248/bpb.35.731.


We have developed a strong inhibitor (S252W mutant soluble ectodomain of fibroblast growth factor recptor-2 IIIc, msFGFR2) that binds FGFs strongly and blocks the activation of FGFRs. In vitro, msFGFR2 could inhibit the promoting effect of transforming growth factor (TGF)-β1 on the proliferation of primary lung fibroblasts. In vivo, msFGFR2 alleviated lung fibrosis through inhibiting the expression of α-smooth muscle actin (SMA) and collagen deposit. In Western blotting of the right lung tissues and immunohistochemical assay, we found the level of p-FGFRs, p-mitogen activated protein kinase (MAPK) and p-Smad3 in the mice of bleomycin (BLM) group treated with msFGFR2 was down dramatically compared with the mice of BLM group, which suggested the activations of FGF and TGF-β signals were blocked meanwhile. In summary, msFGFR2 attenuated BLM-induced fibrosis and is an attractive therapeutic candidate for human pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Bleomycin
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Fibroblast Growth Factors / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Lung / drug effects*
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / prevention & control*
  • Receptor, Fibroblast Growth Factor, Type 2 / pharmacology
  • Receptor, Fibroblast Growth Factor, Type 2 / therapeutic use*
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*


  • Actins
  • Peptide Fragments
  • Receptors, Fibroblast Growth Factor
  • Recombinant Proteins
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta1
  • msFGFR2 protein
  • Bleomycin
  • Fibroblast Growth Factors
  • Collagen
  • Receptor, Fibroblast Growth Factor, Type 2
  • Mitogen-Activated Protein Kinases