MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1
MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1
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MiR-495 通过靶向 Bmi-1 促进间充质干细胞衰老
DOI：
10.1159/000478069
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Zhao, Guangfeng
中科院分区：
文献类型：
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作者：
Li, Xiujun;Song, Yuxian;Zhao, Guangfeng
背景/目的：间充质干细胞（MSCs）在调节血管生成和免疫平衡中发挥重要作用。在子痫前期（PE）患者的母胎界面中，有报告称MSC的异常增殖和功能。已知Micro-RNA-495在来自PE患者的MSC中上调。然而，目前尚不清楚miR-495的上调是否与PE的发病机制有关。研究方法：我们分析了miR-495在健康妊娠（NC）和PE来源的MSC和脐带中的表达，然后上调或下调NC来源的MSC中miR-495的表达，并检测其增殖、凋亡、迁移、侵袭、管形成和衰老。结果如下：在本研究中，我们发现miR-495在重度PE患者的脐带组织和MSC中的表达显著增加。过表达miR-495可使细胞周期阻滞于S期，促进细胞凋亡。miR-495过表达的MSCs培养上清抑制MSCs和HTR-8/SVneo的迁移、HTR-8/SVneo的侵袭和HUVEC的管腔形成，而si-miR-495则相反。进一步分析衰老相关的β-半乳糖苷酶活性和CD 146，发现miR-495诱导MSCs衰老。分子机制研究证实Bmi-1介导了miR-495对MSCs的这些作用。结论：miR-495诱导的MSCs衰老可能参与了PE的发病机制。
Background/Aims: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.