MiR-483 induces senescence of human adipose-derived mesenchymal stem cells through IGF1 inhibition
MiR-483 induces senescence of human adipose-derived mesenchymal stem cells through IGF1 inhibition
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MiR-483 通过抑制 IGF1 诱导人脂肪间充质干细胞衰老
DOI：
10.18632/aging.103818
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发表时间：
2020-08-15
期刊：
影响因子：
5.2
通讯作者：
Liu, Hailiang
中科院分区：
文献类型：
--
作者：
Shen, Junyan;Zhu, Xiaoqi;Liu, Hailiang
人脂肪间充质干细胞(HADSCs)是一种理想的再生和组织工程种子细胞来源。然而，长期的体外培养会降低hADSCs的数量和质量，降低其研究和临床应用的价值。这一生物过程背后的分子机制还不清楚。最近发现的microRNAs(MiRNAs)已经成为细胞衰老的关键调节因子。在这项研究中，我们研究了hADSCs在衰老过程中的变化。HADSCs在体外传代过程中miR-483-3p表达显著上调，与成脂分化和细胞衰老有关。MiR-483-3p基因敲除可延缓hADSCs的成脂分化潜能，减少细胞衰老。经双荧光素酶分析，确定胰岛素样生长因子-1(IGF1)为miR-483-3p的靶基因。IGF1抑制证实了其对hADSCs复制衰老的抑制作用。总之，我们的研究揭示了miR-483-3p通过靶向IGF1在hADSCs的脂肪形成和衰老中的重要调节作用。
Human adipose-derived mesenchymal stem cells (hADSCs) are an ideal source of seed cells for regenerative applications and tissue engineering. However, long-term in vitro culture of hADSCs reduces their quantity and quality, which lessens their value in research and clinical applications. The molecular mechanisms underlying this biological process are poorly defined. Recently identified microRNAs (miRNAs) have emerged as critical modulators of cellular senescence. In this study, we examined the changes in hADSCs undergoing senescence. Significant miR-483-3p upregulation was noted during in vitro passaging of hADSCs, which correlated with the adipogenic differentiation and cellular senescence. Knockdown of miR-483-3p retarded the adipogenic differentiation potential of hADSCs and reduced cellular senescence. Dual-luciferase reporter assays identified insulin-like growth factor-1 (IGF1) as the target gene of miR-483-3p. IGF1 inhibition confirmed its inhibitory effects on replicative senescence in hADSCs. In conclusion, our study revealed essential regulatory roles of miR-483-3p in the adipogenesis and aging of hADSCs mediated by targeting IGF1.