Possible molecular target uncovered for prevention of keloid scarring
MedWire News: Collagen triple helix repeat containing-1 protein (CTHRC1) inhibits the transforming growth factor (TGF)-β1-stimulated collagen production that occurs in keloid scar formation, report researchers.
"Keloids are manifestations of an abnormal process of tissue repair after trauma to the skin. Options for treatment are limited because of lack of understanding of the molecular and cellular mechanisms governing the formation," explain Hongxiang Chen (Huazhong University of Science and Technology, Wuhan, China) and colleagues.
"Increased understanding of the role of TGF-β signaling in keloids makes manipulation of TGF-β an attractive therapeutic strategy," they say.
CTHRC1 is expressed in the adventitia and neointima on arterial injury. Chen and team assessed regulation of the CTHRC1 gene, its interaction with TGF-β1, and its possible role in keloid scar formation in fibroblast cells from keloid tissue and normal skin.
TGF-β1 and CTHRC1 were localized to the dermis in both normal and keloid skin fibroblasts. Expression of both factors were increased in keloid compared with normal skin and CTHRC1 appeared to increase in a TGF-β1 concentration-dependent manner.
When keloid fibroblasts were treated with TGF-β1 (10 ng/ml), cell proliferation increased dramatically, specifically, collagen type I synthesis was preferentially stimulated.
However, when recombinant CTHRC1 was added to the TGF-β1-treated keloid cells, the proliferation effect was reversed and excess collagen synthesis was inhibited.
Notably, treatment with recombinant CTHRC1 appeared to have no adverse effects on cell viability.
"Our data indicated that TGF-β1 was overexpressed in keloid fibroblasts and recombinant CTHRC1 could reverse TGF-β1-induced collagen type I expression at least in part by decreasing collagen synthesis," conclude the authors.
"As a potent negative regulator of collagen matrix deposition, CTHRC1 may have therapeutic value in antifibrotic treatment strategies," they suggest.
The results of this study are published in the British Journal of Dermatology.
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By Helen Albert