Keratinocyte growth factor decreases pulmonary edema, transforming growth factor-beta and platelet-derived growth factor-BB expression, and alveolar type II cell loss in bleomycin-induced lung injury

Inflammation. 1998 Jun;22(3):315-25. doi: 10.1023/a:1022304317111.


Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and mortality in a rat model of bleomycin-induced lung injury. In this study, protective effects of KGF were explored during the earlier course of bleomycin-induced lung injury by studying protein exudation in alveolar edema fluids, pulmonary expression of transforming growth factor-beta (TGF beta) and platelet-derived growth factor-BB (PDGF-BB), and changes in type II pneumocytes and Clara cells after i.t. (intratracheal) bleomycin injection following KGF- or saline-pretreatment in rats. Total protein in bronchoalveolar lavage (BAL) fluids after bleomycin injury from KGF-pretreated rats was significantly lower than the levels in saline-pretreated rats. TGF beta protein in BAL fluids which peaked at day 3 after i.t. bleomycin in saline-pretreated lungs was not significantly increased at any time points in KGF-pretreated rats. PDGF-BB protein in whole lung tissues of KGF-pretreated rats also remained near normal throughout the course after i.t. bleomycin, in contrast to the significant increase in saline-pretreated rats. Numbers of type II pneumocytes and Clara cells in KGF-pretreated lungs after a high dose of bleomycin were close to the normal in intact lungs. At the same dose of bleomycin injury, type II pneumocytes in saline-pretreated lungs were markedly decreased, while the number of Clara cells in these rats was relatively preserved as the pre-injury level. In conclusion, KGF prevents bleomycin-induced end-stage pulmonary injury and mortality probably at least partly by decreasing protein-rich pulmonary edema, protein expression of fibrogenic cytokines TGF beta and PDGF-BB, and type II cell loss during the course of lung injury.

MeSH terms

  • Animals
  • Becaplermin
  • Bleomycin
  • Bronchoalveolar Lavage Fluid / chemistry
  • Exudates and Transudates / metabolism
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Growth Substances / pharmacology*
  • Humans
  • Lung / pathology
  • Platelet-Derived Growth Factor / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-sis
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology*
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / metabolism*
  • Pulmonary Edema / pathology*
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins
  • Transforming Growth Factor beta / metabolism*


  • FGF7 protein, human
  • Fgf7 protein, rat
  • Fibroblast Growth Factor 10
  • Growth Substances
  • Platelet-Derived Growth Factor
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Bleomycin
  • Fibroblast Growth Factor 7
  • Becaplermin
  • Fibroblast Growth Factors