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J Dermatol Sci. 2012 Jan;65(1):38-49. doi: 10.1016/j.jdermsci.2011.09.012. Epub 2011 Oct 17.

Wnt/β-catenin pathway forms a negative feedback loop during TGF-β1 induced human normal skin fibroblast-to-myofibroblast transition.

Author information

1
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China.

Abstract

BACKGROUND:

Fibroblast-to-myofibroblast transition is a key event during wound healing and hypertrophic scar formation. Previous studies suggested Wnt/β-catenin signaling might be involved in the wound healing. However, its specific role in skin fibroblast-to-myofibroblast transition remains unclear.

OBJECTIVE:

To investigate the specific role of β-catenin during the transforming growth factor-β1 induced normal skin myofibroblasts transition.

METHODS:

By real-time quantitative polymerase chain reaction, Western-blot and immunocytochemistry, the activation of Wnt/β-catenin pathway in cultured human normal skin fibroblasts during TGF-β1 induced fibroblast-to-myofibroblast transition was investigated. The effects of β-catenin on myofibroblasts transition were also investigated when SB-216763, over-expression and siRNA of β-catenin were utilized. In addition, fibroblasts populated collagen lattices contraction assays were conducted to examine the effects of β-catenin on the contractility of the fibroblasts induced by TGF-β1. Furthermore, the effects of β-catenin on the expression of α-smooth muscle actin and collagen types I and III in hypertrophic scar derived fibroblasts were studied.

RESULTS:

The expression of Wnts mRNA and β-catenin protein was up-regulated by TGF-β1 stimulation during the myofibroblasts transition. Both of SB-216763 and β-catenin over-expression was paralleled with decreased expression of α-smooth muscle actin, collagen types I and III, while siRNA targeting β-catenin leads to up-regulation of α-smooth muscle actin, collagen types I and III. The increased contractility and α-smooth muscle actin expression of the fibroblasts in the collagen lattices induced by TGF-β1 was inhibited by SB-216763. In addition, the expression levels of α-smooth muscle actin, collagen types I and III in hypertrophic scar derived fibroblasts were also down-regulated by SB-216763.

CONCLUSION:

Specifically in normal skin fibroblasts, β-catenin might be involved in the myofibroblasts transition and negatively regulate the TGF-β1-induced myofibroblast transition.

PMID:
22041457
DOI:
10.1016/j.jdermsci.2011.09.012
[Indexed for MEDLINE]

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