TY - JOUR
T1 - Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin
AU - Fumagalli, Mara
AU - Musso, Tiziana
AU - Vermi, William
AU - Scutera, Sara
AU - Daniele, Roberta
AU - Alotto, Daniela
AU - Cambieri, Irene
AU - Ostorero, Alessia
AU - Gentili, Francesca
AU - Caposio, Patrizia
AU - Zucca, Mario
AU - Sozzani, Silvano
AU - Stella, Maurizio
AU - Castagnoli, Carlotta
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Activin A
KW - Follistatin
KW - Hypertrophicscar
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U2 - 10.1111/j.1600-0625.2007.00571.x
DO - 10.1111/j.1600-0625.2007.00571.x
M3 - Article
C2 - 17576240
AN - SCOPUS:34250782560
SN - 0906-6705
VL - 16
SP - 600
EP - 610
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 7
ER -