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.%目的:研究年龄相关microRNA-486-5p (miR-486-5p)对人骨髓间充质干细胞(hMSCs)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hMSCs 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hMSCs衰老的影响;通过siRNA研究沉默信息调节因子1(SIRT1)对hMSCs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,hMSCs中miR-486-5p的表达增加。过表达miR-486-5p可促进hMSCs衰老。相反,抑制miR-486-5p的表达可减少hMSCs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hMSCs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hMSCs端粒酶活性,促进hMSCs衰老。
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