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Dexamethasone induced miR-155 up-regulation in differentiating 3T3-L1 preadipocytes does not affect adipogenesis

机译:地塞米松诱导分化3T3-L1前脂肪细胞中的miR-155上调不影响脂肪形成

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摘要

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.
机译:地塞米松是一种合成的糖皮质激素,在鼠和人体外模型中广泛用作成脂诱导剂。糖皮质激素已经显示出调节脂肪形成中的早期转录事件。 MicroRNA(miRNA)也参与了前脂肪细胞分化的调控。然而,尚未研究糖皮质激素对这一过程中miRNA表达水平的影响。在这项研究中,我们研究了糖皮质激素对miR-155在分化3T3-L1前脂肪细胞中表达水平的影响。我们发现,在分化3T3-L1前脂肪细胞中,糖皮质激素上调了miR-155的水平(2.4倍),并且在糖皮质激素受体拮抗剂RU486的存在下,这种增强作用被消除。相反,用另一种成脂诱导剂罗格列酮治疗可降低这些细胞中miR-155的表达水平。此外,我们的数据显示内源性miR-155不太可能参与脂肪形成,因为我们显示地塞米松和罗格列酮都诱导脂肪形成达到相似水平。此外,使用miR-155抑制剂,我们显示地塞米松介导的miR-155增强不会改变脂肪形成。我们的数据显示,地塞米松而非罗格列酮增加了miR-155的表达,而miR-155的表达增加并未参与3T3-L1模型中地塞米松介导的脂肪形成。

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