Serum Amyloid A3 Gene Expression in Adipocytes is an Indicator of the Interaction with Macrophages.

Serum Amyloid A3 Gene Expression in Adipocytes is an Indicator of the Interaction with Macrophages.
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DOI:
10.1038/srep38697
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发表时间:
2016-12-08
期刊:
影响因子:
4.6
通讯作者:
Yanaka N
Yanaka N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sanada Y;Yamamoto T;Satake R;Yamashita A;Kanai S;Kato N;van de Loo FA;Nishimura F;Scherer PE;Yanaka N

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巨噬细胞向脂肪组织的浸润及其与脂肪细胞的相互作用是肥胖脂肪组织慢性低度炎症的必要条件。在本研究中,我们发现血清淀粉样蛋白A3 (Saa3)基因是与巨噬细胞相互作用影响的关键脂肪细胞衍生因子。我们发现脂肪细胞中的Saa3启动子实际上对共培养系统中活化的巨噬细胞有反应。3T3-L1脂肪细胞中C/EBPβ丰度的降低或C/EBPβ元件的点突变抑制了巨噬细胞激活时启动子活性的增加,提示C/EBPβ在Saa3启动子激活中起重要作用。基于Saa3-luc小鼠Saa3启动子活性的生物发光在肥胖脂肪组织中得到促进,表明Saa3启动子活性很可能与巨噬细胞浸润有关。本研究提示,Saa3基因的表达水平可用于肥胖脂肪组织中浸润巨噬细胞的数量。
The infiltration of macrophages into adipose tissue and their interaction with adipocytes are essential for the chronic low-grade inflammation of obese adipose tissue. In this study, we identified the serum amyloid A3 (Saa3) gene as a key adipocyte-derived factor that is affected by interaction with macrophages. We showed that the Saa3 promoter in adipocytes actually responds to activated macrophages in a co-culture system. Decreasing C/EBPβ abundance in 3T3-L1 adipocytes or point mutation of C/EBPβ elements suppressed the increased promoter activity in response to activated macrophages, suggesting an essential role of C/EBPβ in Saa3 promoter activation. Bioluminescence based on Saa3 promoter activity in Saa3-luc mice was promoted in obese adipose tissue, showing that Saa3 promoter activity is most likely related to macrophage infiltration. This study suggests that the level of expression of the Saa3 gene could be utilized for the number of infiltrated macrophages in obese adipose tissue.
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