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- Title
Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin.
- Authors
Fumagalli, Mara; Musso, Tiziana; Vermi, William; Scutera, Sara; Daniele, Roberta; Alotto, Daniela; Cambieri, Irene; Ostorero, Alessia; Gentili, Francesca; Caposio, Patrizia; Zucca, Mario; Sozzani, Silvano; Stella, Maurizio; Castagnoli, Carlotta
- 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.
- Subjects
HYPERTROPHIC scars; SKIN diseases; SKIN inflammation; CYTOKINES; GROWTH factors; TRANSFORMING growth factors; FOLLISTATIN
- Publication
Experimental Dermatology, 2007, Vol 16, Issue 7, p600
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2007.00571.x