剥脱综合征患者房水蛋白质组学分析  

Proteomic analysis of aqueous humor in patients with exfoliation syndrome

作　　者：徐钊 王礼明 冯强[2] 张丹丹 阿依古再丽 郭如如 东莉洁[1] 魏瑞华[1] 刘爱华 Xu Zhao;Wang Liming;Feng Qiang;Zhang Dandan;Ayiguzaili Tuerdimaimaiti;Guo Ruru;Dong Lijie;Wei Ruihua;Liu Aihua(Tianjin Key Laboratory of Retinal Functions and Diseases,Tianjin Branch of National Clinical Research Center for Ocular Disease,Eye Institute and School of Optometry,Tianjin Medical University Eye Hospital,Tianjin 300384,China;Department of Ophthalmology,People's Hospital of Hotan District,Hotan Perfecture 848000,China)

机构地区：[1]天津医科大学眼科医院,天津医科大学眼视光学院,天津医科大学眼科研究所,国家眼耳鼻喉疾病临床医学研究中心,天津市分中心天津市视网膜功能与疾病重点实验室,天津300384 [2]和田地区人民医院眼科,和田848000

出　　处：《中华实验眼科杂志》2024年第6期512-519,共8页Chinese Journal Of Experimental Ophthalmology

基　　金：新疆维吾尔自治区自然科学基金面上项目(2020D01A06);天津医科大学眼科医院临床研究中心青年专项基金(2020QN02);天津市医学重点学科(专科)建设项目(TJYXZDXK-037A)。

摘　　要：目的分析剥脱综合征(XFS)患者房水蛋白质的表达差异。方法收集2020年6月至2021年1月在和田地区人民医院拟行手术治疗的维吾尔族年龄相关性白内障患者和XFS伴白内障患者各10例,分别作为白内障组和XFS组。术中借助超声乳化手术通道吸取前房中部50~100μl房水。通过非标记定量蛋白质组学质谱分析技术对房水中提取的蛋白进行分析,以白内障组作为对照组,并根据P<0.05、差异倍数>1.5的标准筛选得到XFS组的差异表达蛋白。通过基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)信号通路分析来探讨XFS组差异表达蛋白的功能及调控信号通路。结果与白内障组相比,XFS组共鉴定出25个差异表达蛋白,这些蛋白主要涉及细胞黏附、受体、水解酶、分子运输等。表达下调的蛋白有14个,包括补体H因子相关蛋白1(CFHR1)、内质网分子伴侣BiP(HSPA5)、双糖链蛋白多糖(BGN)、FRAS1相关的细胞外基质蛋白2(FREM2)、血红蛋白亚基δ(HBD)、血红蛋白亚单位γ1(HBG1)、棕榈酰蛋白水解酶2(PPT2)等。表达上调的蛋白有11个,包括转化生长因子结合蛋白2(LTBP2)、极低密度脂蛋白受体、层粘连蛋白亚基α2(LAMA2)、凝血因子Ⅸ(F9)等。其中,FREM2为XFS组差异表达最显著的蛋白,其在XFS组个体样本中表达水平基本一致。GO分析显示,这些差异蛋白主要定位于胶原蛋白的细胞外基质、结合珠蛋白-血红蛋白复合物、血浆脂蛋白颗粒和溶酶体腔;分子功能和生物学过程显示,HBD和HBG1参与细胞解毒过程,PPT2参与水解酶活性,BGN和LTBP2参与糖胺聚糖结合。KEGG信号通路分析显示,CFHR1和F9参与补体和凝血级联通路;FREM2和LAMA2参与细胞外基质相互作用通路。结论XFS的进展可能与细胞外基质蛋白的改变、血-房水屏障破坏以及潜在的炎症反应有关。显著下调的FREM2可能作为XFS潜在的生物学标志物。Objective To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome(XFS).Methods A total of 20 patients were enrolled in the Department of Ophthalmology,People's Hospital of Hotan District from June 2020 to January 2021,including 10 patients with age-related cataract and 10 XFS patients combined with cataract,which were classified as cataract group and XFS group,respectively.A total of 50 to 100μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group,and the differentially expressed proteins(DEPs)in XFS group were screened according to P<0.05 and fold change>1.5.Gene ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital(No.2020KY[L]-21).Written informed consent was obtained from each subject.Results In comparison with the cataract group,25 DEPs were identified in the XFS group,primarily involved in cell adhesion,receptor,hydrolase,and molecular transport.Specifically,there were 14 down-regulated proteins including complement factor H-related protein 1(CFHR1),endoplasmic reticulum chaperone BiP(HSPA5),biglycan(BGN),FRAS1-related extracellular matrix protein 2(FREM2),hemoglobin subunit delta(HBD),hemoglobin subunit gamma-1(HBG1),lysosomal thioesterase PPT2(PPT2)etc.,and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2(LTBP2),very low-density lipoprotein receptor(VLDLR),laminin subunit alpha-2(LAMA2),coagulation factorⅨ(F9).Among them,FREM2 was the most significantly differentially expressed protein in XFS group with co

关 键 词：剥脱综合征 房水 蛋白质组学 FRAS1相关的细胞外基质蛋白2 生物学信息分析 

分 类 号：R779.6[医药卫生—眼科]