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

Mara 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

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40 Scopus citations

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- β, play an important role in this process. Activin A, a member of the TGF- β family, shares the same intra-cellular Smad signalling pathway with TGF- β, 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 α-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-βs stimulation. We demonstrate that fibroblasts do express activin receptors, and that this expression is not affected by TGF-βs. Treatment of HS fibroblasts with activin A induced Akt phosphorylation, promoted cell proliferation, and enhanced α-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.

Original languageEnglish (US)
Pages (from-to)600-610
Number of pages11
JournalExperimental Dermatology
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2007

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Keywords

  • Activin A
  • Follistatin
  • Hypertrophicscar

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Fumagalli, M., Musso, T., Vermi, W., Scutera, S., Daniele, R., Alotto, D., Cambieri, I., Ostorero, A., Gentili, F., Caposio, P., Zucca, M., Sozzani, S., Stella, M., & Castagnoli, C. (2007). Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin. Experimental Dermatology, 16(7), 600-610. https://doi.org/10.1111/j.1600-0625.2007.00571.x