慢性家族性良性天疱疮患者病变皮肤的蛋白质组学分析  

Proteome Changes of Skin Lesions from Patients with Benign Chronic Familial Pemphigus

作　　者：张鼎伟[1] 霍佳[1] 李晓莉[1] 王媛[1] 黄颖 马迎新 崔鹿 ZHANG Dingwei;HUO Jia;LI Xiaoli;WANG Yuan;HUANG Ying;MA Yingxin;CUI Lu(Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院皮肤科

出　　处：《中国皮肤性病学杂志》2019年第12期1347-1353,共7页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金(81803161);西安交通大学自由探索与创新项目(Xjj2018137)

摘　　要：目的了解慢性家族性良性天疱疮(HHD)患者皮肤的蛋白质组学变化。方法收集HHD患者以及对照正常皮肤组织,进行iTRAQ定量蛋白质组学分析。使用ATP2C1特异性siRNA转染人原代角质形成细胞。收集皮肤组织或ATP2C1 siRNA转染的人原代角质形成细胞,使用Western blot以及RT-PCR对iTRAQ分析的差异蛋白进行表达验证。结果iTRAQ共鉴定到134个在HHD患者组织中发生显著差异表达的蛋白质。对这些差异表达的蛋白质进行GO分析以及KEGG分析,123个显著匹配的注释蛋白参与187个已知的KEGG代谢或信号通路。HHD患者组织中差异表达的蛋白主要参与PI3K-Akt信号通路,黏着斑,细胞外基质(ECM)-受体相互作用,蛋白质降解与吸收等。结论HHD患者病变组织中差异表达的蛋白质主要与细胞黏附,ECM-受体相互作用,以及蛋白质折叠及糖基化相关,提示靶向细胞连接以及细胞外微环境可能为改善HHD的治疗提供新策略。Objective To demonstrate the proteomic changes in skin lesions in benign chronic familial pemphigus(or Hailey-Hailey disease,HHD)patients.Methods Samples of skin lesions from HHD patients and healthy volunteers were collected for iTRAQ analysis.ATP2C1-specific siRNAs were transfected into human primary keratinocytes.Western blotting and RT-PCRwere applied to validate the results of iTRAQ-processed proteins.Results A total of 134 proteins from all three HHD patients were differentially expressed.These differentially expressed proteins were assigned to Gene Ontology(GO)term and the Kyoto Encyclopedia of Genes and Genomes(KEGG),and 123 annotated proteins with significant matches were assigned to 187 known metabolic or signaling pathways listed in KEGG.Most of the altered proteins were enriched in the PI3K-Akt signaling,focal adhesion,ECM-receptor interaction,and protein digestion and absorption.Conclusion The differentially expressed proteins related to cell adhesion,ECM-receptor interaction,and protein folding and glycosylation,suggesting that strategies targeting cell junction and extracellular microenvironment may provide a potential treatment for HHD.

关 键 词：慢性家族性良性天疱疮 蛋白质组学 ATP2C1 原代角质形成细胞 

分 类 号：R758.66[医药卫生—皮肤病学与性病学]