Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Cell Biochem. 2011 Feb;112(2):488-97. doi: 10.1002/jcb.22936.
Signal transducer and activator of transcription 3 (STAT3) was reported to be involved in adipogenesis. However, the regulating mechanism of STAT3 remains unclear. The present results showed that STAT3 was activated within 2-h adipogenic induction, in which the phosphorylated STAT3 translocated from cytoplasm to the nucleus. In addition, we detected Janus kinase2 (JAK2) acted upstream of the STAT3 activation at the early stage of adipogenesis. Accordingly, the JAK2 inhibitor AG490 and siRNAs led to the partial inhibition of the STAT3 activation, and the inhibition of 3T3-L1 adipocyte differentiation. Furthermore, the results based on luciferase, chromatin immunoprecipitation, and gel shift approaches indicated that STAT3 could regulate the transcription of C/EBPβ by binding the distal region of C/EBPβ promoter at the early stage of adipogenesis. Collectively, our findings reveal that JAK2/STAT3 pathway is involved in the early stage of 3T3-L1 adipocyte differentiation though regulating the C/EBPβ transcription.
信号转导子和转录激活子 3(STAT3)被报道参与脂肪生成。然而,STAT3 的调节机制尚不清楚。本研究结果表明,STAT3 在 2 小时的诱导脂肪生成过程中被激活,其中磷酸化的 STAT3 从细胞质转位到细胞核。此外,我们检测到在脂肪生成的早期阶段,Janus 激酶 2(JAK2)作为 STAT3 激活的上游分子。因此,JAK2 抑制剂 AG490 和 siRNAs 导致 STAT3 激活的部分抑制,并抑制 3T3-L1 脂肪细胞分化。此外,基于荧光素酶、染色质免疫沉淀和凝胶迁移实验的结果表明,STAT3 可以通过结合脂肪生成早期 C/EBPβ 启动子的远端区域来调节 C/EBPβ 的转录。综上所述,我们的研究结果表明,JAK2/STAT3 通路通过调节 C/EBPβ 的转录,参与 3T3-L1 脂肪细胞分化的早期阶段。