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Molecular biological analysis of the Wnt signal pathway in keloid development

瘢痕疙瘩发生过程中Wnt信号通路的分子生物学分析

基本信息

批准号：
15591906
负责人：
TOSA Mamiko
金额：
$ 2.18万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591906/
关键词：
keloid fibloblasts Wnt signal β-catenin axin β-catenin 遺伝子解析線維芽細胞

项目摘要

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.

瘢痕疙瘩是一种病因不明的真皮纤维增生性病变。WNT信号通路在调节细胞生长和分化中起着重要作用。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。我们首先研究了Wnt信号通路下游靶基因β-catenin和Axin在瘢痕疙瘩成纤维细胞和正常真皮成纤维细胞中的表达差异。β-连环蛋白在KF中高表达，而β-连环蛋白抑制基因Axin在KF中低表达。免疫组织化学分析证实β-catenin在KF中高表达，Axin在KF中低表达。为了研究Wnt信号通路的功能特性，我们研究了细胞外基质相关基因在NF和KF中的表达。我们检测了两个主要的细胞外基质分子COL1A2和FN1mRNA在β-catenin多肽处理后在KF和NF中的表达。加入β-Catenin多肽后，NF和KF的COL1A2和FN1mRNA表达均增加。提示活化的Wnt信号通路通过促进成纤维细胞ECM相关基因的表达参与了瘢痕疙瘩的发病过程。