SRPX2经uPAR调控人单核细胞系THP-1来源巨噬细胞迁移及M2极化  

Role of SRPX2/uPAR in controlling human monocytes THP-1 originated macrophage migration and M2 polarization

作　　者：刘揆亮 李楠杉 吴静 李文坤 李倩 劳月琼 LIU Kui-liang;LI Nan-shan;WU Jing;LI Wen-kun;LI Qian;LAO Yue-qiong(Department of Gastroenterology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院消化内科

出　　处：《基础医学与临床》2019年第10期1432-1436,共5页Basic and Clinical Medicine

基　　金：北京市自然科学基金(7184220,7162090);北京市优秀人才培养项目(2017000021469G257);北京市医管局<青苗>计划(QML20170704)

摘　　要：目的评价SRPX2蛋白对人单核细胞系THP-1来源巨噬细胞迁移及极化功能的影响。方法经佛波酯(PMA)诱导人单核细胞系THP-1为巨噬细胞后,将SRPX2重组蛋白作用于巨噬细胞,Transwell法检测细胞迁移,免疫荧光法检测SRPX2与uPAR的定位,Western blot检测相应信号通路蛋白的表达。再用IFN-γ及LPS诱导巨噬细胞的M1极化,SRPX2重组蛋白作用后,反转录PCR检测M1/M2标志物表达。结果SRPX2明显促进人单核细胞系THP-1来源巨噬细胞的迁移(P<0.01),加入uPAR中和抗体后,明显抑制迁移(P<0.01)。在诱导M1极化的巨噬细胞中,经SRPX2重组蛋白作用后,M1标志物CD40和IL-6明显下降,而M2标志物CD206和IL-6明显上升(P<0.01)。SRPX2与uPAR及CD11b的表达存在共定位。SRPX2重组蛋白作用后巨噬细胞FAK及Akt磷酸化水平增高。结论SRPX2可能通过uPAR/CD11b/FAK/Akt通路促进人单核细胞THP-1来源巨噬细胞的迁移与M2极化。Objective To investigate the effect of SRPX2 protein on migration and polarization of human monocytes THP-1 derived macrophages. Methods PMA was used to induce macrophages derived from human THP-1 cells. Transwell, immunoflurescence and Western blot were used to determine the cell immigration, signal protein level and location of SRPX2 and uPAR respectively. after SRPX2 been added, IFN-γ and LPS were used to induce M1 polarization cells, RT-PCR was used to measure M1/M2 markers. Results The migration of THP-1 derived macrophages was significantly increased by SRPX2(P<0.01) and antagonized by uPAR neutralization antibody(P<0.01). SRPX2 markedly promoted the expression of CD206/IL-6, while decreased the expression of CD40/IL-6(both P<0.01). The colocalization of SRPX2/uPAR/CD11 b was confirmed. The phosphorylation of FAK and Akt was activated by SRPX2. Conclusions SRPX2 may promote the migration and M2 polarization of human monocytes THP-1 originated macrophage via uPAR/CD11 b/FAK/Akt pathway.

关 键 词：含SUSHI重复蛋白X连锁2(SRPX2) 尿激酶型纤溶酶原激活物受体 巨噬细胞 迁移 极化 

分 类 号：R392.9[医药卫生—免疫学]