Premium
Matrix contraction by dermal fibroblasts requires syndecan 4: Insights into pathological scarring in chronic fibrotic disease
Author(s) -
Leask Andrew,
Kennedy Laura,
Chen Yunliang,
Shiwen Xu,
WilcoxAdelman Sarah,
Goetinck Paul,
Black Carol M,
Abraham David J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1098-c
Subject(s) - fibrosis , extracellular matrix , pathological , syndecan 1 , medicine , pathology , contraction (grammar) , disease , myofibroblast , dermis , fibroblast , microbiology and biotechnology , biology , cell , genetics , cell culture
Chronic fibrotic diseases, such as diffuse systemic sclerosis (dSSc), are characterized by excessive scarring. The cell type that causes scarring is the myofibroblast. We show that fibroblasts isolated from scars of dSSc patients retain their myofibroblast phenotype in cell culture. We find that antagonizing transforming growth factor‐beta receptor type I with the specific ALK5 inhibitor SB431542 alleviates the elevated matrix contraction by dSSc fibroblasts. dSSc fibroblasts show elevated ERK activation, and antagonizing MEK with U0126 suppresses the contractile abilities of dSSc dermal fibroblasts. TGFbeta‐induced matrix contraction requires the proteglycan syndecan 4, as TGFbeta cannot induce a contractile phenotype in syndecan 4 −/ − dermal fibroblasts or induce phosphorylation of ERK. Lesional dSSc fibroblasts overexpress syndecan 4. Syndecan 4 siRNA reduces the activated phenotype of SSc fibroblasts. Thus antagonizing syndecan 4 would be expected to alleviate scarring in chronic fibrotic diseases, including dSSc.