溃疡性结肠炎发病、疾病活动和生物治疗疗效相关基因CRELD2的生物信息学分析  

Bioinformatics Analyses of Gene CRELD2 that Associated with Pathogenesis,Disease Activity and Efficacy of Biological Agents in Ulcerative Colitis

作　　者：陶文惠[1] 王帆[1] 林雪[1] 马敏星 赵秋[1] 李瑾[1] TAO Wenhui WANG Fan LIN Xue MA Minxing ZHAO Qiu LI Jin(Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei Clinical Center ＆ Key Lab of lntestinal and Colorectal Diseases, Wuhan （430071)

机构地区：[1]武汉大学中南医院消化内科湖北省肠病医学临床研究中心、肠病湖北省重点实验室,430071

出　　处：《胃肠病学》2017年第1期4-9,共6页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金青年科学基金项目(81200283)

摘　　要：背景:应用生物信息学方法能有效挖掘基因芯片数据,并对单基因功能进行预测分析。目的:对与溃疡性结肠炎(UC)发病、疾病活动和生物治疗疗效相关的CRELD2基因进行生物信息学分析,为深入研究该基因的生物学功能及其参与UC发生、发展的分子机制提供理论依据。方法:从基因表达综合数据库(GEO数据库)中下载UC发病、疾病活动和生物治疗疗效相关基因芯片数据,应用BRB-ArrayT ools、ProtP aram、ELM、SignalP 4.1、PBIL-IBCP Lyon Gerland、GO、STRING等生物信息学工具进行数据挖掘和分析。结果:交叉分析显示,在UC发病、疾病活动中进行性表达增高,同时在英夫利昔单抗治疗有效后表达明显降低的基因共有4个,分别为CDC25B、CRELD2、IL1RN、PITPNC1,其中CRELD2基因功能未知。生物信息学分析显示,人CRELD2基因位于染色体22q13.33,编码由402个氨基酸残基组成的分泌型蛋白。CRELD2蛋白含有多个表皮生长因子(EGF)样结构域,主要分布于高尔基体、内质网和细胞外,主要参与钙离子结合和蛋白结合,与CHRNA4、CHRNB2、RHBDD3等蛋白之间存在相互作用。结论:CRELD2可能具有类似EGF的功能,并可能通过直接或间接参与免疫细胞的调控对UC发病、疾病活动产生影响,有望成为UC诊断、疾病活动性评估、疗效评估的新指标和新的治疗靶点。Bioinformatics is an effective technology for microarray data mining and gene function prediction. Aims ： To analyze the gene CRELD2 that associated with pathogenesis, disease activity and efficacy of biological agents in ulcerative colitis （UC） by bioinformatics to provide a theoretical basis for subsequent studies on its biological function and molecular mechanism in the development and progress of UC. Methods： The microarray data associated with pathogenesis, disease activity and efficacy of biological agents in UC were downloaded from the Gene Expression Omnibus （GEO database）; the data mining and analyses were conducted by using bioinformatics tools such as BRB-ArrayTools, ProtParam, ELM, SignalP 4.1, PBIL-IBCP Lyon Gerland, GO and STRING. Results： Cross-over analyses revealed that expressions of four genes （CDC25B, CRELD2, ILl RN, PITPNC1 ） were up-regulated in the order from colonic mucosa of healthy subjects, un-inflamed mucosa of active UC patients to inflamed mucosa of active UC patients, meanwhile these four genes were significantly down-regulated in infliximab responders after treatment when compared with that before treatment and infliximab non-responders. The function of CRELD2 gene was unknown. Bioinformatics analyses showed that CRELD2 gene was located on the long arm of chromosome 22 （22q13. SS）, and encoded a secreted protein composed of 402 amino acids. This protein contained several epidermal growth factor （EGF）-like domains, mainly distributed in Golgi apparatus, endoplasmic reticulum and extracellular site and had calcium- and protein-binding effect. Interactions existed between CRELD2 and CHRNA4, CHRNB2 and RHBDD3 proteins. Conclusions： Gene CRELIY2 may have EGF-like biological function and via participating directly or indirectly the regulation of immunocytes to affect the pathogenesis and disease activity of UC. It might be used as a biomarker for diagnosis and assessment of disease activity and therapeutic efficacy of UC. Furthermore, it might be a potential t

关 键 词：CRELD2基因 结肠炎 溃疡性 生物信息学 微阵列分析 

分 类 号：R574.62[医药卫生—消化系统]