Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin

Exp Dermatol. 2007 Jul;16(7):600-10. doi: 10.1111/j.1600-0625.2007.00571.x.


Hypertrophic scarring is a skin disorder characterized by persistent inflammation and fibrosis that may occur after wounding or thermal injury. Altered production of cytokines and growth factors, such as TGF-beta, play an important role in this process. Activin A, a member of the TGF-beta family, shares the same intra-cellular Smad signalling pathway with TGF-beta, but binds to its own specific transmembrane receptors and to follistatin, a secreted protein that inhibits activin by sequestration. Recent studies provide evidences of a novel role of activin A in inflammatory and repair processes. The aim of this study was to evaluate the importance of activin A and follistatin expression in the different phases of scar evolution. Immunostaining of sections obtained from active phase hypertrophic scars (AHS) revealed the presence of a high number of alpha-SMA(+) myofibroblasts and DC-SIGN(+) dendritic cells coexpressing activin A. Ex-vivo AHS fibroblasts produced more activin and less follistatin than normal skin or remission phase hypertrophic scar (HS) fibroblasts, both in basal conditions and upon TGF-betas stimulation. We demonstrate that fibroblasts do express activin receptors, and that this expression is not affected by TGF-betas. Treatment of HS fibroblasts with activin A induced Akt phosphorylation, promoted cell proliferation, and enhanced alpha-SMA and type I collagen expression. Follistatin reduced proliferation and suppressed activin-induced collagen expression. These results indicate that the activin/follistatin interplay has a role in HS formation and evolution. The impact of these observations on the understanding of wound healing and on the identification of new therapeutic targets is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Activin Receptors / metabolism
  • Activins / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Burns / complications
  • Burns / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cicatrix, Hypertrophic / etiology
  • Cicatrix, Hypertrophic / metabolism*
  • Cicatrix, Hypertrophic / pathology
  • Dendritic Cells / metabolism
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / physiology
  • Follistatin / metabolism*
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / metabolism
  • Skin / pathology
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / physiology


  • Actins
  • Follistatin
  • Transforming Growth Factor beta1
  • activin A
  • Activins
  • Activin Receptors