Overexpression of fibroblast growth factor-10 during both inflammatory and fibrotic phases attenuates bleomycin-induced pulmonary fibrosis in mice

Am J Respir Crit Care Med. 2009 Sep 1;180(5):424-36. doi: 10.1164/rccm.200811-1794OC. Epub 2009 Jun 4.


Rationale: Fibroblast growth factor-10 (FGF10) controls survival, proliferation, and differentiation of distal-alveolar epithelial progenitor cells during lung development.

Objectives: To test for the protective and regenerative effect of Fgf10 overexpression in a bleomycin-induced mouse model of pulmonary inflammation and fibrosis.

Methods: In SP-C-rtTA; tet(O)Fgf10 double-transgenic mice, lung fibrosis was induced in 2-month-old transgenic mice by subcutaneous delivery of bleomycin (BLM), using an osmotic minipump for 1 week. Exogenous Fgf10 expression in the alveolar epithelium was induced for 7 days with doxycycline during the first, second, and third weeks after bleomycin pump implantation, and lungs were examined at 28 days.

Measurements and main results: Fgf10 overexpression during Week 1 (inflammatory phase) resulted in increased survival and attenuated lung fibrosis score and collagen deposition. In these Fgf10-overexpressing mice, an increase in regulatory T cells and a reduction in both transforming growth factor-beta(1) and matrix metalloproteinase-2 activity were observed in bronchoalveolar lavage fluids whereas the number of surfactant protein C (SP-C)-positive, alveolar epithelial type II cells (AEC2) was markedly elevated. Analysis of SP-C and TUNEL (terminal deoxynucleotidyltransferase dUTP nick end labeling) double-positive cells and isolation of AEC2 from lungs overexpressing Fgf10 demonstrated increased AEC2 survival. Expression of Fgf10 during Weeks 2 and 3 (fibrotic phase) showed significant attenuation of the lung fibrosis score and collagen deposition.

Conclusions: In the bleomycin model of lung inflammation and fibrosis, Fgf10 overexpression during both the inflammatory and fibrotic phases results in a greatly reduced extent of lung fibrosis, suggesting that FGF10 may be useful as a novel approach to the treatment of pulmonary fibrosis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic
  • Bleomycin
  • Disease Models, Animal
  • Doxycycline
  • Fibroblast Growth Factor 10 / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Pneumonia / chemically induced
  • Pneumonia / metabolism*
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Reference Values
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Transforming Growth Factor beta1 / drug effects
  • Transforming Growth Factor beta1 / metabolism


  • Antibiotics, Antineoplastic
  • Fgf10 protein, mouse
  • Fibroblast Growth Factor 10
  • Transforming Growth Factor beta1
  • Bleomycin
  • Doxycycline