miR-486-5p通过抑制端粒酶活性促进人骨髓间充质干细胞衰老  

miR-486-5p enhances senescence of human mesenchymal stem cells by decreasing telomerase activity

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

机构地区：[1]广州医科大学附属第二医院,广东广州510260 [2]广州心血管疾病研究所,广东广州510260

出　　处：《中国病理生理杂志》2015年第3期547-551,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年科学基金资助项目(No.81401156);广州市医药卫生科技项目(No.20141A011088);广州医科大学博士科研项目(No.2013C49)

摘　　要：目的:研究年龄相关microRNA-486-5p(miR-486-5p)对人骨髓间充质干细胞(h MSCs)衰老的调控作用。方法:通过microRNA芯片和real-time PCR检测供体年龄对h MSCs中miR-486-5p表达的影响;通过转染miR-486-5p模拟物或抑制物,过表达miR-486-5p或抑制其表达;用β-半乳糖苷酶染色检测miR-486-5p对h MSCs衰老的影响;通过siRNA研究沉默信息调节因子1(SIRT1)对h MSCs端粒酶逆转录酶(TERT)、端粒酶活性及衰老的影响。结果:随供体年龄增加,h MSCs中miR-486-5p的表达增加。过表达miR-486-5p可促进h MSCs衰老。相反,抑制miR-486-5p的表达可减少h MSCs的衰老。SIRT1及TERT随供体年龄增加而表达下降,直接抑制SIRT1的表达可减少TERT表达,抑制端粒酶活性,促进细胞衰老。同时抑制miR-486-5p和SIRT1的表达,使miR-486-5p失去对h MSCs端粒酶活性及衰老的调控作用。结论:miR-486-5p通过抑制SIRT1,减少h MSCs端粒酶活性,促进h MSCs衰老。AIM：To investigate the effects of microRNA-486-5p （miR-486-5p） on the senescence of human mesenchymal stem cells （ hMSCs）.METHODS： The expression of miR-486-5p was determined by miRNA arrays and real-time PCR.By transfection of miR-486-5p mimic or inhibitor, up-regulation or down-regulation of miR-486-5p expres-sion in hMSCs was established.The effect of miR-486-5p and silence information regulator 1 （SIRT1） on hMSC telomerase activity and senescence were detected byβ-galactosidase staining.RESULTS：The expression of miR-486-5p was up-regu-lated in the old hMSCs compared with the young hMSCs.Up-regulation of miR-486-5p resulted in increasing senescence of hMSCs.Conversely, down-regulation of miR-486-5p resulted in decreasing cell senescence.The expression of SIRT1 and telomerase reverse transcriptase （ TERT） was down-regulated in the old hMSCs compared with the young hMSCs.Directly repression of SIRT1 expression inhibited the hMSC TERT protein expression and telomerase activity, but increased cell se-nescence.The regulation of miR-486-5p on hMSC senescence was attenuated by inhibiting the expression of miR-486-5p and SIRT1 together.CONCLUSION：miR-486-5p enhances senescence of hMSCs by decreasing the expression of SIRT1 and telomerase activity.

关 键 词：人骨髓间充质干细胞 MicroRNA-486-5p 衰老 

分 类 号：R363[医药卫生—病理学] R339.38[医药卫生—基础医学]