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

Abstract
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.
AuthorsMara Fumagalli, Tiziana Musso, William Vermi, Sara Scutera, Roberta Daniele, Daniela Alotto, Irene Cambieri, Alessia Ostorero, Francesca Gentili, Patrizia Caposio, Mario Zucca, Silvano Sozzani, Maurizio Stella, Carlotta Castagnoli
JournalExperimental dermatology (Exp Dermatol) Vol. 16 Issue 7 Pg. 600-10 (Jul 2007) ISSN: 0906-6705 [Print] Denmark
PMID17576240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Follistatin
  • Transforming Growth Factor beta1
  • activin A
  • Activins
  • Activin Receptors
Topics
  • Actins (metabolism)
  • Activin Receptors (metabolism)
  • Activins (metabolism)
  • Adolescent
  • Adult
  • Aged
  • Burns (complications, metabolism)
  • Cell Proliferation
  • Cells, Cultured
  • Cicatrix, Hypertrophic (etiology, metabolism, pathology)
  • Dendritic Cells (metabolism)
  • Female
  • Fibroblasts (metabolism, physiology)
  • Follistatin (metabolism)
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin (metabolism, pathology)
  • Transforming Growth Factor beta1 (metabolism)
  • Wound Healing (physiology)

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