Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
Aging (Albany NY). 2020 Aug 15;12(15):15756-15770. doi: 10.18632/aging.103818.
Human adipose-derived mesenchymal stem cells (hADSCs) are an ideal source of seed cells for regenerative applications and tissue engineering. However, long-term 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 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 () as the target gene of miR-483-3p. 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 .
人脂肪间充质干细胞（hADSCs）是再生应用和组织工程中种子细胞的理想来源。然而，hADSCs 的长期培养会降低其数量和质量，从而降低其在研究和临床应用中的价值。这一生物学过程的分子机制尚不清楚。最近发现的 microRNAs（miRNAs）已成为细胞衰老的关键调节因子。在这项研究中，我们研究了衰老过程中 hADSCs 的变化。在 hADSCs 的传代过程中观察到 miR-483-3p 的显著上调，这与成脂分化和细胞衰老相关。miR-483-3p 的敲低会降低 hADSCs 的成脂分化潜能并减少细胞衰老。双荧光素酶报告基因实验鉴定出胰岛素样生长因子-1（IGF-1）是 miR-483-3p 的靶基因。IGF-1 抑制证实了其对 hADSCs 复制性衰老的抑制作用。总之，我们的研究揭示了 miR-483-3p 通过靶向 IGF-1 在 hADSCs 成脂分化和衰老中的重要调节作用。
