miR-708-5p通过抑制TMEM88表达促进人骨髓间充质干细胞迁移  

miR-708-5p accelerates migration of human mesenchymal stem cells by repressing TMEM88 expression

作　　者：黎佼[1,2] 刘宁宁[1] 胡明[2] 曾波航[3] 董珺[1,3] 刘世明[1,2] 

机构地区：[1]广州医科大学附属第二医院广州心血管疾病研究所,广东广州510260 [2]广州医科大学附属第二医院心内科,广东广州510260 [3]广州医科大学附属第二医院肿瘤科,广东广州510260

出　　处：《中国病理生理杂志》2015年第2期239-244,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年基金资助项目(No.81401156);广州市医药卫生科技项目(No.20141A011088)

摘　　要：目的:研究年龄相关microRNA-708-5p(miR-708-5p)对人骨髓间充质干细胞(h MSCs)迁移能力的调控作用。方法:通过microRNA芯片和real-time PCR检测供体年龄对h MSCs中miR-708-5p表达的影响;通过转染miR-708-5p模拟物或抑制物,过表达或抑制miR-708-5p表达;通过细胞划痕及Transwell实验检测h MSCs迁移能力。通过siRNA研究miR-708-5p靶基因跨膜蛋白88(TMEM88)对h MSCs中β链球蛋白(β-catenin)及h MSCs迁移功能的影响。结果:随供体年龄增加,h MSCs中miR-708-5p的表达下降。过表达miR-708-5p可促进h MSCs迁移。相反,抑制miR-708-5p的表达可减少h MSCs迁移。随供体年龄增加,TMEM88表达增加,而β-catenin表达下降,直接抑制TMEM88的表达可促进β-catenin表达,促进h MSCs迁移。同时抑制miR-708-5p和TMEM88,使miR-708-5p失去对h MSCs的调控作用。结论:miR-708-5p可通过抑制TMEM88表达,上调β-catenin,从而活化Wnt/β-catenin信号通路,促进h MSCs迁移。AIM： To investigate the effect of microRNA-708-5p（ miR-708-5p） on the migration of human mesenchymal stem cells（ h MSCs）. METHODS： The expression of miR-708-5p was determined by miRNA arrays and real-time PCR. By transfection of miR-708-5p mimic or inhibitor,the up-regulation or down-regulation of miR-708-5p expression in h MSCs was evaluated. The cell scratch and Transwell tests were used to detect the migration capability of h MSCs. The effects of transmembrane protein 88（ TMEM88）,a miR-708-5p target gene,on β-catenin expression and migration of h MSCs were detected. RESULTS： The expression of miR-708-5p was down-regulated in the old h MSCs compared with the young h MSCs. Up-regulation of miR-708-5p resulted in increasing migration of h MSCs. Conversely,down-regulation of miR-708-5p resulted in decreasing cell migration. The expression of TMEM88 was up-regulated in the old h MSCs compared with the young h MSCs,while the expression of β-catenin was down-regulated. Directly repression of TMEM88 expression increased the β-catenin expression and migration of h MSCs. The regulation of miR-708-5p on h MSCs was attenuated by inhibiting the expression of miR-708-5p and TMEM88 together. CONCLUSION： miR-708-5p increases β-catenin expression and Wnt / β-catenin activity by repressing TMEM88,thus enhancing the migration of h MSCs.

关 键 词：人骨髓间充质干细胞 MicroRNA-708-5p 年龄 细胞迁移 

分 类 号：R363[医药卫生—病理学]