Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice

Am J Respir Crit Care Med. 2005 Jun 1;171(11):1279-85. doi: 10.1164/rccm.200404-531OC. Epub 2005 Feb 25.


Imatinib mesylate is a potent and specific tyrosine kinase inhibitor against c-ABL, BCR-ABL, and c-KIT, and has been demonstrated to be highly active in chronic myeloid leukemia and gastrointestinal stromal tumors. We examined the antifibrotic effects of imatinib using a bleomycin-induced lung fibrosis model in mice because imatinib also inhibits tyrosine kinase of platelet-derived growth factor receptors (PDGFRs). Imatinib inhibited the growth of primary murine lung fibroblasts and the autophosphorylation of PDGFR-beta induced by PDGF. Administration of imatinib significantly prevented bleomycin-induced pulmonary fibrosis in mice, partly by reducing the number of mesenchymal cells incorporating bromodeoxyuridine. Analysis of bronchoalveolar lavage cells demonstrated that imatinib did not suppress early inflammation on Days 7 and 14 caused by bleomycin. These results suggest that imatinib has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that imatinib might be useful for the treatment of pulmonary fibrosis in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides
  • Bleomycin
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal
  • Female
  • Fibroblasts / drug effects
  • Imatinib Mesylate
  • Intracellular Signaling Peptides and Proteins / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Piperazines / therapeutic use*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / pathology
  • Pyrimidines / therapeutic use*
  • Reference Values
  • Treatment Outcome


  • Benzamides
  • Intracellular Signaling Peptides and Proteins
  • Piperazines
  • Pyrimidines
  • protein kinase modulator
  • Bleomycin
  • Imatinib Mesylate