Liu Yitong, Guo Lijia, Hu Lei, Xie Chen, Fu Jingfei, Jiang Yiyang, Han Nannan, Jia Lu, Liu Yi
Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, China.
Department of Orthodontics School of Stomatology, Capital Medical University, China.
Stem Cells Int. 2020 Dec 10;2020:8866048. doi: 10.1155/2020/8866048. eCollection 2020.
The adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) plays an important role in the process of obesity and host metabolism. D-Mannose shows a potential regulating function for fat tissue expansion and glucose metabolism. To explore the mechanisms through which D-mannose affects the adipogenic differentiation of adipose-derived stem cells , we cultured the ADSCs with adipogenic medium inducement containing D-mannose or glucose as the control. The adipogenic differentiation specific markers and were determined by real-time PCR. The Oil Red O staining was applied to measure the lipid accumulation. To further explore the mechanisms, microarray analysis was performed to detect the differences between glucose-treated ADSCs (G-ADSCs) and D-mannose-treated ADSCs (M-ADSCs) in the gene expression level. The microarray data were further analyzed by a Venn diagram and Gene Set Enrichment Analysis (GSEA). MicroRNA inhibitor transfection was used to confirm the role of key microRNA. . D-Mannose intervention significantly inhibited the adipogenic differentiation of ADSCs, compared with the glucose intervention. Microarray showed that D-mannose increased the expression of miR669b, which was an inhibitor of adipogenesis. In addition, GSEA and western blot suggested that D-mannose suppressed the adipogenic differentiation inhibiting the MAPK pathway and further inhibited the expression of proteins related to glucose metabolism and tumorigenesis. . D-Mannose inhibits adipogenic differentiation of ADSCs the miR669b/MAPK signaling pathway and may be further involved in the regulation of glucose metabolism and the inhibition of tumorigenesis.
脂肪组织来源干细胞（ADSCs）的成脂分化在肥胖和宿主代谢过程中起重要作用。D-甘露糖对脂肪组织扩张和葡萄糖代谢显示出潜在的调节功能。为了探究D-甘露糖影响脂肪来源干细胞成脂分化的机制，我们用含有D-甘露糖的成脂培养基诱导培养ADSCs，并以葡萄糖作为对照。通过实时PCR测定成脂分化特异性标志物。应用油红O染色来测量脂质积累。为了进一步探究机制，进行微阵列分析以检测葡萄糖处理的ADSCs（G-ADSCs）和D-甘露糖处理的ADSCs（M-ADSCs）在基因表达水平上的差异。通过维恩图和基因集富集分析（GSEA）对微阵列数据进行进一步分析。使用微小RNA抑制剂转染来确认关键微小RNA的作用。与葡萄糖干预相比，D-甘露糖干预显著抑制了ADSCs的成脂分化。微阵列显示D-甘露糖增加了miR669b的表达，miR669b是一种脂肪生成抑制剂。此外，GSEA和蛋白质印迹表明D-甘露糖通过抑制MAPK途径抑制成脂分化，并进一步抑制与葡萄糖代谢和肿瘤发生相关的蛋白质表达。D-甘露糖通过miR669b/MAPK信号通路抑制ADSCs的成脂分化，并且可能进一步参与葡萄糖代谢的调节和肿瘤发生的抑制。
