Molecular biological analysis of the Wnt signal pathway in keloid development

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Keloid is a dermal fibroproliferative lesion of unknown etiology. Wnt signaling pathway plays an important role in the regulation of cell growth and differentiation. Activation of Wnt signaling pathway in keloid fibroblasts (KF) is thought to be closely linked to abnormal cell proliferation and migration. We first examined the difference in mRNA expression of downstream targets in the Wnt signaling pathway namely β-catenin and axin between keloid fibroblasts and normal dermal fibroblasts (NF). The β-catenin was overexpressed in KF, although axin, an inhibitory gene to β-catenin, was suppressed in KF. Immunohistochemical analysis confirmed the high expression of β-catenin and low expression of axin in KF. To examine the functional properties of the Wnt signaling pathway, we then investigated extracellular matrix (ECM) related gene expression in both NF and KF.We measured mRNA expressions of two principal ECM molecules, COL1A2 and FN1, in KF and NF after treatment with a β-catenin peptide. COL1A2 and FN1 mRNA expressions after addition of β-catenin peptide were increased in both NF and KF. These findings suggested the involvement of activated Wnt signal pathway in the pathogenesis of keloid sacr via enhancing the ECM-related gene expression in fibroblasts.