Molecular biological analysis of the Wnt signal pathway in keloid development

瘢痕疙瘩是一种病因不明的皮肤纤维增生性病变。Wnt信号通路在细胞生长和分化的调控中起着重要作用。瘢痕疙瘩成纤维细胞（KF）中Wnt信号通路的激活被认为与细胞的异常增殖和迁移密切相关。我们首先检查了瘢痕疙瘩成纤维细胞和正常皮肤成纤维细胞（NF）之间Wnt信号通路中下游靶标即β-连环蛋白和轴蛋白的mRNA表达的差异。β-catenin在KF中过表达，而β-catenin的抑制基因axin在KF中被抑制。免疫组化证实KF中β-catenin高表达，axin低表达。为了检测Wnt信号通路的功能特性，我们研究了NF和KF中细胞外基质（ECM）相关基因的表达。我们测量了用β-连环蛋白肽处理后KF和NF中两种主要ECM分子COL 1A 2和FN 1的mRNA表达。加入β-catenin肽后，NF和KF中的COL 1A 2和FN 1 mRNA表达均增加。提示Wnt信号通路的激活可能通过增强成纤维细胞ECM相关基因的表达而参与瘢痕疙瘩的发病过程。

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.