Stimulation of 3T3-L1 adipogenesis by signal transducer and activator of transcription 5
Stimulation of 3T3-L1 adipogenesis by signal transducer and activator of transcription 5
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DOI：
10.1210/me.16.7.1565
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发表时间：
2002-07-01
影响因子：
--
通讯作者：
Wakao, H
中科院分区：
文献类型：
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作者：
Nanbu-Wakao, R;Morikawa, Y;Wakao, H
信号转导子和转录激活子 5 (Stat5) 介导许多细胞因子和生长因子的信号传导。在这里，我们展示了 Stat5 作为脂肪生成的初始调节剂。前脂肪细胞系 3T3-L1 在适当的激素诱导下经历脂肪细胞分化。我们发现 Stat5A 和 Stat5B 在 3T3-L1 分化的早期阶段被强烈激活。为了研究 Stat5 在脂肪生成中的生理作用，我们构建了 3T3-L1 细胞系，其中外源野生型 (wt) 或显性失活 (dn) 形式的 Stat5A 表达受强力霉素调节启动子的控制。 wt-Stat5A 在脂肪细胞分化中的过早诱导促进了细胞内甘油三酯的积累。相反，dn-Stat5A 的诱导减弱了脂质积累。 Northern印迹分析表明，促脂肪生成转录因子的表达以互补的方式受到wt-或dn-Stat5A异位表达的影响。值得注意的是，Stat5 调节过氧化物酶体增殖物激活受体-γ 的表达，这在脂肪形成中起着至关重要的作用。我们还培育了转基因小鼠，其中 dn-Stat5A 以脂肪组织特异性方式表达，并发现过氧化物酶体增殖物激活受体 γ 和许多脂肪细胞相关基因的减弱。这些结果强调了 Stat5 在脂肪细胞分化中的新作用。
Signal transducer and activator of transcription 5 (Stat5) mediates signaling of many cytokines and growth factors. Here we show that Stat5 functions as an initial mediator of adipogenesis. The preadipocyte cell line 3T3-L1 undergoes adipocyte differentiation upon appropriate hormonal induction. We found that Stat5A and Stat5B were strongly activated at an early stage of 3T3-L1 differentiation. To investigate physiological roles of Stat5 in adipogenesis, we have constructed 3T3-L1 cell lines in which either an exogenous wild type (wt) or dominant negative (dn) form of Stat5A expression was controlled under the doxycycline-regulatable promoter. Precocious induction of wt-Stat5A in adipocyte differentiation promoted accumulation of triglycerides within the cells. In contrast, induction of dn-Stat5A attenuated lipid accumulation. Northern blot analyses revealed that the expression of proadipogenic transcription factors was influenced in a complementary fashion by ectopic expression of either wt- or dn-Stat5A. Notably, Stat5 regulated expression of peroxisome proliferator-activated receptor-gamma, which plays crucial roles in adipogenesis. We have also generated transgenic mice in which dn-Stat5A is expressed in an adipose tissue-specific fashion and found attenuation of peroxisome proliferator-activated receptor-gamma and of many adipocyte-related genes. These results high-light a novel role of Stat5 in adipocyte differentiation.