Notch信号在增生性瘢痕表皮中的表达  

Expression of Notch receptors, ligands and downstream target genes in epidermis of hypertrophic scar

作　　者：夏炜[1] 潘宝华[1] 刘宾[1] 张曦[1] 马福成[2] 王映梅[2] 杨晓婷[2] 刘丹[1] 郭树忠[1] 

机构地区：[1]第四军医大学西京医院整形外科研究,西安710032 [2]第四军医大学西京医院病理科,西安710032

出　　处：《中华整形外科杂志》2009年第1期41-45,共5页Chinese Journal of Plastic Surgery

基　　金：国家自然科学基金资助（30371469,30801190）;陕西省科技厅资助（2006C253）

摘　　要：目的研究Notch信号相关分子在增生性瘢痕表皮中的表达情况，探讨其是否参与增生性瘢痕的形成。方法收集年龄、性别、部位互为对照的增生性瘢痕和健康皮肤组织各8例。行免疫组织化学检测：①表皮分化标志物，包括整合素β1、角蛋白14（K14）和19（K19）；②Notch受体1～4以及配体Jagged1。行Real-timePCR和免疫组织化学检测Notch下游基因P21和P63的表达以及定位。结果组织学检测发现增生性瘢痕表皮较健康表皮明显增厚，基底上层细胞层数显著增多。表皮干细胞标志整合素岛、基底细胞层短暂扩充细胞标志K19和有丝分裂后细胞标志K14的表达在增生性瘢痕表皮中明显减少（P〈0．05）。增生性瘢痕Notch1和Jagged1表达在基底上层角质形成细胞中阳性细胞明显多于健康皮肤（P〈0．05）。增生性瘢痕表皮P21表达较正常表皮增多，而P63表达则明显降低（P〈0．05）。结论增生性瘢痕角质形成细胞表达过量的受体Notch1和配体Jagged1，通过上调下游基因P21表达，下调P63基因表达，刺激瘢痕表皮过度分化，从而参与增生性瘢痕的形成。Objective To study the expression of Notch receptors, ligands and downstream target genes in hypertrophic scar and normal skin, and to investigate its role in the development of hypertrophic scar. Methods By immunohistochemistry, the expression of epidermal differentiation markers-β1 integrin, keratin 14 （K14） and keratin 19 （K19）, as well as Notch 1-4 and Jaggedl were examined in hypertrophic scars and normal skins. The expression of Notch downstream genes- P21 and P63 was analyzed with real-time quantitative PCR and immunohistochemistry staining. Results Histological analysis revealed a significant epidermal thickening in the hypertrophic scars, with excessive cell layers above the basal layer. Compared to the normal epidermis, the expression of 61 integrin, K19 and K14 decreased in hypertrophic scars （P 〈 0.05）. Positive expression rate of Notchl and Jaggedl in keratinocytes was significantly higher in hypertrophic scar than in normal skin （P 〈 0.05）, while there was no difference in Notch2 and 3 positive expression rate. Furthermore, the expression of P21 was significantly up-regulated, while the expression of P63 was down-regnlated in keratinocytes of hypertrophic scar （ P 〈 0.05 ）. Conclusions Notch signal may play an important role in hypertrophic scar pathogenesis. Over-defferentiation of Keratinocytes in hypertrophic scar may be related to the overexpression of Notchl and Jaggedl, up-regulation of P21 gene and down-regulation of P63 gene.

关 键 词：瘢痕 NOTCH信号途径 患者 基因表达 

分 类 号：R622[医药卫生—整形外科]