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TNFα 诱导的 miR-155 上调抑制脂肪生成,通过下调早期脂肪生成转录因子。

TNFα-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors.

机构信息

Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Biochem Biophys Res Commun. 2011 Oct 28;414(3):618-24. doi: 10.1016/j.bbrc.2011.09.131. Epub 2011 Oct 2.

Abstract

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.

摘要

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。

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