The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo

PLoS One. 2013;8(4):e59966. doi: 10.1371/journal.pone.0059966. Epub 2013 Apr 2.

Abstract

Hypertrophic scars (HTS) and keloids are challenging problems. Their pathogenesis results from an overproduction of fibroblasts and excessive deposition of collagen. Studies suggest a possible anti-scarring effect of basic fibroblast growth factor (bFGF) during wound healing, but the precise mechanisms of bFGF are still unclear. In view of this, we investigated the therapeutic effects of bFGF on HTS animal model as well as human scar fibroblasts (HSF) model. We show that bFGF promoted wound healing and reduced the area of flattened non-pathological scars in rat skin wounds and HTS in the rabbit ear. We provide evidence of a new therapeutic strategy: bFGF administration for the treatment of HTS. The scar elevation index (SEI) and epidermal thickness index (ETI) was also significantly reduced. Histological reveal that bFGF exhibited significant amelioration of the collagen tissue. bFGF regulated extracellular matrix (ECM) synthesis and degradation via interference in the collagen distribution, the α-smooth muscle actin (α-SMA) and transforming growth factor-1 (TGF-β1) expression. In addition, bFGF reduced scarring and promoted wound healing by inhibiting TGFβ1/SMAD-dependent pathway. The levels of fibronectin (FN), tissue inhibitor of metalloproteinase-1 (TIMP-1) collagen I, and collagen III were evidently decreased, and matrix metalloproteinase-1 (MMP-1) and apoptosis cells were markedly increased. These results suggest that bFGF possesses favorable therapeutic effects on hypertrophic scars in vitro and in vivo, which may be an effective cure for human hypertrophic scars.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Apoptosis / drug effects
  • Cicatrix, Hypertrophic / drug therapy
  • Collagen Type I / biosynthesis
  • Collagen Type III / biosynthesis
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Models, Animal
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rabbits
  • Rats
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / drug effects*
  • Wound Healing / physiology*

Substances

  • Actins
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Collagen Type I
  • Collagen Type III
  • Proliferating Cell Nuclear Antigen
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Fibroblast Growth Factor 2

Grant support

This work was supported by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (to J.X.), State Key Basic Research Development Program (2012CB518105), Zhejiang Provincial Project of Key Group (2010R50042), Ninbo City Natural Science Foundation (R2090550), and Zhejiang Natural Science Foundation (Z2080985). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.