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.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

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

doi

10.1111/j.1600-0625.2007.00571.x

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

600-10

issue

7

eissn

0906-6705

issn

1600-0625

pii

EXD571

journal_volume

16

pub_type

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