咪喹莫特抑制病理性瘢痕成纤维细胞迁移及作用靶点的相关机制  

Mechanism by which imiquimod inhibits the migration of fibroblasts in pathological scars and its targets

作　　者：王瑞[1] 吕涛 霍晶[1] 刘振东[1,2] 宋建波[1] Wang Rui;Lyu Tao;Huo Jing;Liu Zhendong;Song Jianbo(Dezhou People’s Hospital,Dezhou 253000,Shandong Province,China;Clinical School of Yangzhou University/Subei People’s Hospital,Yangzhou 225001,Jiangsu Province,China)

机构地区：[1]德州市人民医院,山东省德州市253000 [2]扬州大学临床医学院/苏北人民医院,江苏省扬州市225001

出　　处：《中国组织工程研究》2022年第20期3173-3177,共5页Chinese Journal of Tissue Engineering Research

基　　金：山东省医药卫生科技发展计划面上项目(202004121375),项目负责人:王瑞;山东省医药卫生科技发展计划面上项目(2019WS017),项目负责人:吕涛。

摘　　要：背景:研究表明咪喹莫特对病理性瘢痕具有一定的防治作用,但其作用靶点及确切机制尚未明确。目的:探索咪喹莫特作用于病理性瘢痕的靶点基因并进行验证,观察咪喹莫特对瘢痕成纤维细胞迁移能力的影响。方法:从GEO在线数据库中下载并分析数据集,整合筛选出咪喹莫特作用于瘢痕组织的靶点基因。提取瘢痕来源的成纤维细胞,采用划痕实验及Transwell实验检测咪喹莫特对细胞迁移能力的影响,免疫印迹法检测Ⅰ型胶原及作用靶点PCOLCE的蛋白表达水平。结果与结论:①通过筛选数据集整合结果,获得2个作用靶点基因,分别为PCOLCE和ARHGEF25;②体外细胞实验结果显示,同对照组相比,咪喹莫特处理组可明显降低细胞划痕愈合率和细胞迁移数目(P<0.05),瘢痕成纤维细胞Ⅰ型胶原和PCOLCE的蛋白表达水平也明显下降(P<0.05);③结果证实,咪喹莫特抑制瘢痕的作用可能与其下调PCOLCE表达水平、减少细胞外基质以及降低细胞迁移率相关。BACKGROUND:Studies have shown that imiquimod has a certain prevention and therapeutic effect on pathological scar,but its target and exact mechanism are not clear yet.OBJECTIVE:To explore and verify the target genes of imiquimod acting on pathological scar,and to observe the effect of imiquimod on the migration ability of scar fibroblasts.METHODS:Data sets were downloaded from GEO online database and analyzed to screen out the target genes of imiquimod acting on scar tissue.Scar-derived fibroblasts were extracted.The effect of imiquimod on cell migration was detected by cell scratch test and Transwell test.The expression of type 1 collagen and PCOLCE was detected by western blot assay.RESULTS AND CONCLUSION:By screening the results of data set integration,two target genes,PCOLCE and ARHGEF25,were obtained.The results of cell experiment in vitro showed that compared with the control group,imiquimod treatment group significantly decreased the scratch healing rate and the number of migrated cells(P<0.05),and the protein expression levels of type I collagen and PCOLCE in scar fibroblasts were also significantly decreased(P<0.05).The results confirmed that the inhibitory effect of imiquimod on scar may be related to its down-regulation of PCOLCE expression,reduction of extracellular matrix,and reduction of cell migration rate.

关 键 词：咪喹莫特 病理性瘢痕 成纤维细胞 胶原蛋白 细胞迁移 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学]