REGULATION OF TRANSCRIPTION FACTOR ALPHA-RNA ACCUMULATION DURING 3T3-L1 PREADIPOCYTE DIFFERENTIATION BY TUMOR-NECROSIS-FACTOR-ALPHA
REGULATION OF TRANSCRIPTION FACTOR ALPHA-RNA ACCUMULATION DURING 3T3-L1 PREADIPOCYTE DIFFERENTIATION BY TUMOR-NECROSIS-FACTOR-ALPHA
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DOI：
10.1677/jme.0.0090061
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发表时间：
1992-08-01
影响因子：
3.5
通讯作者：
PEKALA, PH
中科院分区：
文献类型：
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作者：
STEPHENS, JM;BUTTS, MD;PEKALA, PH
3 T3-L1前脂肪细胞分化为具有脂肪细胞生化特性的细胞;肿瘤坏死因子-α（TNF）减弱该过程。这种细胞因子被认为是在转录水平介导的分化抑制，已经通过检查在分化过程的前24小时期间六种转录因子和三种diprotein调节基因的mRNA的积累来研究。在诱导分化后，观察到c-fos和jun-B mRNA的快速和主要积累，其在4-6小时内恢复到接近基础水平。相反，c-jun mRNA，虽然在诱导分化迅速表达，在整个时间过程中保持在相对恒定的水平。暴露于5 nM TNF的细胞增强了所有三种mRNA的积累，但最显著的是c-jun（12倍），在治疗后至少24 h保持升高。在对照分化细胞中，krox-20和fos-B在30 min至2 h短暂表达，而fra-1 mRNA在1至8 h的延长期内积累。同样，TNF增强了这些mRNA的积累。C/EBP，一种转录因子，建议控制参与终末分化状态的基因表达的mRNA的积累，被减弱后暴露的细胞TNF。白细胞介素-6（IL-6）mRNA表达短暂（30分钟至2小时），再次短暂（诱导分化后8小时）。TNF处理显著增强IL-6信使的积累。我们建议，一个或多个转录因子的细胞含量增加或C/EBP的抑制可能是负责的细胞暴露于TNF诱导的分化衰减。
3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumour necrosis factor-alpha (TNF) attenuates this process. Inhibition of differentiation by this cytokine, thought to be mediated at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and three diversely regulated genes during the first 24 h of the differentiation process. Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA, which returned to near basal levels within 4-6 h, was observed. In contrast, c-jun mRNA, although rapidly expressed at the induction of differentiation, remained at relatively constant levels throughout the time-course. Exposure of the cells to 5 nM TNF potentiated the accumulation of all three mRNAs but most significantly that of c-jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fos-B were expressed transiently from 30 min to 2 h, while fra-1 mRNA accumulated over an extended period of 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control the expression of genes involved in the terminally differentiated state, was attenuated after exposure of the cells to TNF. Interleukin-6 (IL-6) mRNA was expressed briefly (30 min to 2 h) and again transiently (at 8 h after induction of differentiation). TNF treatment markedly enhanced accumulation of IL-6 message. We propose that an increased cellular content of one or more transcription factors or the suppression of C/EBP may be responsible for the attenuation of differentiation induced by exposure of the cells to TNF.