College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, PR China.
Beijing Shuita Aged-vinegar Research Institute for Biosciences, Beijing 102200, PR China.
Biochem Biophys Res Commun. 2014 Aug 22;451(2):329-33. doi: 10.1016/j.bbrc.2014.07.130. Epub 2014 Aug 2.
PU.1, an Ets family transcription factor, was previously demonstrated expressed in 3T3-L1 preadipocytes and had an negative effect on adiopogenesis. However, the underlying mechanism remains elusive. Here, miR-191 was identified as an inhibitor of adipocyte differentiation through targeting the 3' untranslated regions of C/EBPβ, the initial factor in the C/EBPα/β-PPARγ terminal pathway of adipogenic differentiation. MiR-191 suppressed the lipid accumulation by Oil Red O staining and downregulated the levels of adipogenic marker genes PPARγ (P<0.01), aP2 (P<0.01) and FAS (P<0.05). Then, we found that PU.1 overexpression resulted in upregulation of miR-191 and adipogenic inhibition. Likewise, PU.1 overexpression rescued the miR-191 decrease and resisted the adipogenic promotion caused by miR-191 oligonucleotide inhibitor. Collectively, these results revealed that PU.1 promoted miR-191 to suppress adipogenesis 3T3-L1 preadipocyte and indicated a new mechanism of PU.1 inhibiting adipogenesis.
PU.1,一种 Ets 家族转录因子,先前在 3T3-L1 前脂肪细胞中表达,并对脂肪生成有负向作用。然而,其潜在机制仍不清楚。在这里,miR-191 被鉴定为通过靶向 C/EBPβ 的 3'UTR 来抑制脂肪细胞分化的抑制剂,C/EBPβ 是脂肪生成分化的 C/EBPα/β-PPARγ 终末途径中的初始因子。miR-191 通过油红 O 染色抑制脂质积累,并下调脂肪生成标记基因 PPARγ(P<0.01)、aP2(P<0.01)和 FAS(P<0.05)的水平。然后,我们发现 PU.1 过表达导致 miR-191 的上调和脂肪生成抑制。同样,PU.1 过表达挽救了 miR-191 的减少,并抵抗了由 miR-191 寡核苷酸抑制剂引起的脂肪生成促进作用。综上所述,这些结果表明 PU.1 促进了 miR-191 抑制 3T3-L1 前脂肪细胞的脂肪生成,并揭示了 PU.1 抑制脂肪生成的新机制。