Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Biochem Biophys Res Commun. 2011 Oct 28;414(3):618-24. doi: 10.1016/j.bbrc.2011.09.131. Epub 2011 Oct 2.
Tumor necrosis factor α (TNFα) is known to inhibit adipogenesis, but the molecular mechanism of this inhibition remains elusive. In the present study, we found that TNFα-induced inhibition of adipogenesis mainly occurs when 3T3-L1 preadipocytes are treated with TNFα within 2h induction of adipogenesis. We revealed that TNFα treatment results in the up-regulation of miR-155 through the NFκB pathway in 3T3-L1 cells. This overexpression of miR-155 may suppress the expression of C/EBPβ and CREB by directly targeting their 3' untranslated regions (3' UTRs). Importantly, anti-miR-155 reduces the TNFα-induced inhibition of adipogenesis, whereas exogenous expression of mir-155 inhibits adipogenesis. Taken together, these findings reveal a novel role for TNFα in the regulation of anti-adipogenic miRNAs.
肿瘤坏死因子α(TNFα)已知可抑制脂肪生成,但这种抑制的分子机制仍不清楚。在本研究中,我们发现 TNFα 诱导的脂肪生成抑制主要发生在 3T3-L1 前脂肪细胞在诱导脂肪生成的 2 小时内用 TNFα 处理时。我们揭示了 TNFα 处理通过 NFκB 途径导致 3T3-L1 细胞中 miR-155 的上调。这种 miR-155 的过表达可能通过直接靶向它们的 3'非翻译区(3'UTR)来抑制 C/EBPβ 和 CREB 的表达。重要的是,抗 miR-155 减少了 TNFα 诱导的脂肪生成抑制,而外源性表达 mir-155 抑制脂肪生成。总之,这些发现揭示了 TNFα 在调节抗脂肪生成 miRNA 中的新作用。