Trohatou Ourania, Zagoura Dimitra, Orfanos Nikos K, Pappa Kalliopi I, Marinos Evangelos, Anagnou Nicholas P, Roubelakis Maria G
1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .
2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
Stem Cells Dev. 2017 Apr 1;26(7):482-494. doi: 10.1089/scd.2016.0203. Epub 2017 Feb 13.
Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells). MiR-26a was identified in high expression levels in AL cells indicating a critical role in the process of adipogenesis. Overexpression of miR-26a in AF-MSCs led to significant induction of their adipogenic differentiation properties that were altered after miR-26a inhibition. We have demonstrated that miR-26a regulates adipogenesis through direct inhibition of PTEN, which in turn promotes activation of Akt pathway. Also, miR-26a modulates cell cycle during adipogenesis by interacting with Cyclin E1 and CDK6. These results point to the regulatory role of miR-26a and its target genes PTEN, Cyclin E1, and CDK6 in adipogenic differentiation of AF-MSCs, providing a basis for understanding the mechanisms of fat cell development and obesity.
最近的研究结果表明，微小RNA（miRNA）对人间充质干/基质细胞（MSC）的脂肪生成调控网络至关重要。源自羊水的胎儿间充质干细胞（AF-MSC）代表了一群多能干细胞，其特征在于具有广泛的分化特性，可应用于基于细胞的治疗。在本研究中，进行了miRNA微阵列分析，以评估终末分化为脂肪细胞样细胞（AL细胞）的AF-MSC中的miRNA表达。在AL细胞中鉴定出miR-26a高表达，表明其在脂肪生成过程中起关键作用。在AF-MSC中过表达miR-26a导致其成脂分化特性显著诱导，而在抑制miR-26a后这些特性发生改变。我们已经证明，miR-26a通过直接抑制PTEN来调节脂肪生成，PTEN进而促进Akt途径的激活。此外，miR-26a在脂肪生成过程中通过与细胞周期蛋白E1和细胞周期蛋白依赖性激酶6（CDK6）相互作用来调节细胞周期。这些结果表明miR-26a及其靶基因PTEN、细胞周期蛋白E1和CDK6在AF-MSC的成脂分化中的调控作用，为理解脂肪细胞发育和肥胖的机制提供了基础。
