Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by antagonists of adipogenesis.
Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by antagonists of adipogenesis.
复制标题
脂肪生成拮抗剂对 3T3-L1 前脂肪细胞分化过程中转录因子 mRNA 积累的调节。
DOI：
10.1007/bf01076476
复制
发表时间：
1993
影响因子：
4.3
通讯作者：
Bernlohr,DA
中科院分区：
文献类型：
--
作者：
Stephens,JM;Butts,M;Stone,R;Pekala,PH;Bernlohr,DA
3T3-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)、视黄酸（RA）和转化生长因子-β (TGF-β)可减弱这一过程。通过检测六种转录因子和自分泌生长因子白细胞介素6 (IL-6) mRNA的积累，研究了这些被认为是在转录水平上的药物对分化的抑制作用。诱导分化后，c-fos和jun-B mRNA迅速积累，在4-6小时内恢复到接近基础水平。相比之下，c-jun mRNA虽然在诱导分化后迅速表达，但在整个时间过程中保持相对恒定的水平。将细胞暴露于5 nM TNF中，增强了所有3种mrna的积累，但最显著的是c-jun（12倍），在处理后至少24小时保持升高。在对照分化细胞中，kox -20和fox-B在30分钟至2小时内短暂表达，而fra-1 mRNA在1至8小时内积累。同样，TNF增强了这些mRNA的积累。C/EBP是一种控制终分化状态相关基因表达的转录因子，其mRNA的积累在细胞暴露于TNF后减弱。暴露于RA或TGF-β的细胞中，C/EBP的表达也受到抑制。IL-6 mRNA短暂表达（30min - 2h），瞬时表达（诱导分化后8h）。TNF处理显著增强IL-6信息的积累。我们提出，细胞中一种或多种转录因子含量的增加或C/EBP的抑制可能是细胞暴露于TNF， RA和TGF-β诱导的分化衰减的原因。
3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumor necrosis factor-α (TNF), retinoic acid (RA), and transforming growth factor-β (TGF-β), attenuate this process. Inhibition of differentiation by these agents, thought to be at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and the autocrine growth factor interleukin 6 (IL-6). Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA was observed that returned to near basal levels within 4–6 h. In contrast, c-jun mRNA, although rapidly expressed following 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 3 mRNAs but most significantly c-jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fox-B were expressed transiently, 30 min to 2 h, while fra-1 mRNA accumulated over an extended period, 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control expression of genes involved in the terminally differentiated state was attenuated after exposure of the cells to TNF. C/EBP expression was also inhibited in cells exposed to RA or TGF-β. 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 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, RA, and TGF-β.