Environmental Health Science and Research Bureau, Health Canada, 50 Colombine Driveway, Ottawa, Ontario, Canada.
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Sci Rep. 2018 Jan 19;8(1):1264. doi: 10.1038/s41598-018-19704-4.
Dexamethasone is a synthetic glucocorticoid that is widely used as an adipogenic inducer in both murine and human in vitro models. Glucocorticoids have been shown to regulate early transcriptional events in adipogenesis. MicroRNAs (miRNAs) have been also implicated in the regulation of preadipocyte differentiation; however, the effects of glucocorticoids on miRNA expression levels during this process have not been studied. In this study we investigated the effects of glucocorticoids on the expression levels of miR-155 in differentiating 3T3-L1 preadipocytes. We found that miR-155 levels were up-regulated (2.4-fold) by glucocorticoids in differentiating 3T3-L1 preadipocytes, and this enhancement was abolished in the presence of RU486, a glucocorticoid receptor antagonist. In contrast, treatment with rosiglitazone, another adipogenic inducer decreased the expression levels of miR-155 in these cells. Further, our data show that endogenous miR-155 is unlikely to be involved in adipogenesis as we show that both dexamethasone and rosiglitazone induced adipogenesis to similar levels. Furthermore, using miR-155 inhibitor, we showed that the dexamethasone mediated miR-155 enhancement did not alter adipogenesis. Our data show that dexamethasone but not rosiglitazone increases miR-155 expression and that the increased expression of miR-155 is not involved in the dexamethasone-mediated adipogenesis in the 3T3-L1 model.
地塞米松是一种合成的糖皮质激素，广泛用作鼠类和人类体外模型中的脂肪生成诱导剂。糖皮质激素已被证明可调节脂肪生成的早期转录事件。microRNAs (miRNAs) 也参与调节前脂肪细胞分化；然而，糖皮质激素在这个过程中对 miRNA 表达水平的影响尚未得到研究。在这项研究中，我们研究了糖皮质激素对分化的 3T3-L1 前脂肪细胞中 miR-155 表达水平的影响。我们发现 miR-155 的水平在分化的 3T3-L1 前脂肪细胞中被糖皮质激素上调（2.4 倍），并且在存在 RU486（一种糖皮质激素受体拮抗剂）的情况下这种增强被消除。相比之下，另一种脂肪生成诱导剂罗格列酮处理降低了这些细胞中 miR-155 的表达水平。此外，我们的数据表明内源性 miR-155不太可能参与脂肪生成，因为我们表明地塞米松和罗格列酮均诱导脂肪生成到相似水平。此外，使用 miR-155 抑制剂，我们表明地塞米松介导的 miR-155 增强不会改变脂肪生成。我们的数据表明，地塞米松而不是罗格列酮增加 miR-155 的表达，并且 miR-155 的表达增加不参与 3T3-L1 模型中地塞米松介导的脂肪生成。
