Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds

J Pathol. 2004 Jun;203(2):710-20. doi: 10.1002/path.1574.


Cytokines are thought to play an important role in cellular loss and apoptosis during the repair of granulation tissue. In order to investigate the role of apoptosis following the administration of basic fibroblast growth factor (bFGF) to a wound, the present study examined the relationship between the degree of granulation tissue formation and the level of apoptosis in rat skin incisional wounds, following treatment with an intradermal injection of bFGF (0.1 microg and 1 microg per cm of wound). Histological assessment of the width of the wound tissue showed that the degree of granulation tissue in the 1 microg-bFGF-treated group had increased by day 7, but then subsequently diminished by days 14 and 28. The TUNEL index increased rapidly from day 1, peaking on day 7, with the index being higher in the 1 microg-bFGF-treated group on days 4, 7, and 14, when compared with a control group. In parallel with a marked increase in the TUNEL index over the first 14 days, the number of cells positive for vimentin and CD3 in the 1 microg-bFGF-treated wounds had decreased by day 14. The number of PCNA-positive cells, an indicator of cell proliferation, peaked on day 4 in the bFGF-treated wounds and then declined rapidly. On the basis of these results, it is suggested that the suppression of granulation tissue formation in bFGF-treated wounds is mainly due to an early and persistent increase in apoptosis in the granulation tissue cells. The expression of both transforming growth factor (TGF)-beta1 and bFGF was also elevated in the bFGF-treated wounds on days 4 and 7, suggesting that fibroblast apoptosis was induced by bFGF treatment. Unexpectedly, on day 28, the wound breaking strength was not reduced in the bFGF-treated wounds. These results indicate that apoptosis regulation following bFGF administration to an incisional wound may lead effectively to granulation tissue formation and promote a scar-less repair process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / physiology*
  • CD3 Complex / analysis
  • Dermis / physiopathology
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Granulation Tissue / pathology
  • Granulation Tissue / physiopathology*
  • Immunohistochemistry / methods
  • In Situ Nick-End Labeling / methods
  • Injections, Intradermal
  • Proliferating Cell Nuclear Antigen / analysis
  • Rats
  • Rats, Wistar
  • Skin / injuries
  • Skin / physiopathology
  • Transforming Growth Factor beta / analysis
  • Vimentin / analysis
  • Wound Healing / physiology*
  • von Willebrand Factor / analysis


  • CD3 Complex
  • Proliferating Cell Nuclear Antigen
  • Transforming Growth Factor beta
  • Vimentin
  • von Willebrand Factor
  • Fibroblast Growth Factor 2