Wnt2、Wnt3a和β-catenin在硬皮病患者皮损中的作用

Role of Wnt 2,Wnt 3a and β-catenin in skin lesions of patients with scleroderma

目的探讨Wnt/β-catenin信号通路异常活化在硬皮病(SD)发病机制中的作用及其与SD临床分型的关系。方法采用免疫组织化学SP法检测45例SD患者[系统性硬化症(SSc)25例,局限性硬皮病(LSc)20例]皮损中Wnt2、Wnt3a及β-catenin的量与分布,以20例健康成人皮肤作为正常对照(NC)。结果 Wnt2、Wnt3a分别定位于SD患者皮损真、表皮胞浆和胞核,β-catenin定位于真皮类成纤维细胞、外分泌腺上皮细胞及浸润淋巴细胞的胞核及NC、部分SD表皮细胞的胞膜;SD皮损中Wnt2胞浆着色、Wnt3a及β-catenin核着色均显著高于NC(P<0.01),而β-catenin膜着色则明显低于NC(P<0.01);Wnt2、Wnt3a分别与β-catenin核着色呈正相关(r=0.663,0.654,P<0.01),而与β-catenin膜着色呈负相关(r=-0.532,-0.529,P<0.01);SSc上述3种蛋白的着色与LSc间的差异无统计学意义(P>0.05)。结论 SD皮损中存在的异常活化的Wnt/β-catenin信号在其发病机制中可能起重要作用;LSc和SSc分居于SD病谱的两端而非两种独立疾病。

Objective To study the role of abnormally activated Wnt β-catenin signal pathway in the pathogenesis of scleroderma （SD） and its association with the clinical classification of SD. Methods The expression and distribution of Wnt 2, Wnt 3a, and ^-catenin in the skin lesions of 45 SD patients, including 25 with systemic sclerosis （SSc） and 20 with localized scleroderma （LSc）, were detected with SP immunohistochemistry, using 20 samples from healthy skin tissues as normal control. Results In the dermis and epidermis of the SD skin lesions, Wnt 2 and Wnt 3a were located in the cytoplasm and cell nuclei, respectively; ^-catenin was distributed in the nuclei of dermal fibroblast-like ceils, glandular epithelium cells and infiltrating lymphocytes, and on the cell membrane in normal and a part of the affected epidermis. The skin lesions of SD patients showed obviously increased staining intensity of cytoplasmic Wnt 2, nuclear Wnt 3a and β-catenin, but markedly lowered cell membrane staining of β-catenin than normal skins （P〈0.01）. Both Wnt 2 and Wnt 3a were positively correlated with nuclear β-catenin deposition （r=0.663 and 0.654, P〈0.01） and negatively with cell membrane β-catenin staining （r=-0.532 and -0.529, P〈0.01）. No significant difference was found in the staining intensities of the 3 proteins between SSc and LSc （P〉 0.05）. Conclusion Abnormal activation of Wnt/β-catenin pathway occurs in the skin lesions of SD patients, which may play an important role in the pathogenesis of SD. SSc and LSc represent the two opposite ends of the SD spectrum rather than two separate diseases.