RASSF6 expression in adipocytes is down-regulated by interaction with macrophages.
RASSF6 expression in adipocytes is down-regulated by interaction with macrophages.
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DOI：
10.1371/journal.pone.0061931
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yanaka N
中科院分区：
文献类型：
--
作者：
Sanada Y;Kumoto T;Suehiro H;Nishimura F;Kato N;Hata Y;Sorisky A;Yanaka N
巨噬细胞进入脂肪组织与肥胖有关，而脂肪细胞和巨噬细胞之间的串扰是脂肪组织炎症过程中的一个重要病理现象。在这里，我们试图确定脂肪细胞的mRNAs是通过与体内渗透的巨噬细胞的相互作用来调节的。抗炎维生素维生素B6抑制巨噬细胞向白色脂肪组织的渗透，并改变了mRNA的表达。我们确定了在db/db小鼠肥胖发展过程中其表达显著改变的>；3500基因，并将它们与补充维生素B6的小鼠的脂肪组织mRNA表达谱进行了比较。我们发现PTX3和MMP3是受巨噬细胞浸润调控的候选基因。活化的RAW264.7细胞可上调3T3-L1脂肪细胞PTX3和MMP3mRNA的表达，并与体内脂肪组织中巨噬细胞数呈正相关。接下来，我们筛选了与巨噬细胞相互作用下调的脂肪基因，并分离到RASSF6(RAS关联结构域家族6)。激活的RAW264.7细胞条件培养液可使脂肪细胞RASSF6 mRNA表达降低，且RASSF6基因表达水平与脂肪组织中巨噬细胞数呈负相关，提示体内巨噬细胞对脂肪细胞RASSF6基因表达有下调作用。最后，本研究还表明，RASSF6表达降低会上调CD44和高迁移率族蛋白HMGA2等几个基因的mRNA表达。这些数据为肥胖发展过程中脂肪组织中脂肪细胞和巨噬细胞之间相互作用的生物学意义提供了新的见解。
Macrophage infiltration into adipose tissue is associated with obesity and the crosstalk between adipocytes and infiltrated macrophages has been investigated as an important pathological phenomenon during adipose tissue inflammation. Here, we sought to identify adipocyte mRNAs that are regulated by interaction with infiltrated macrophages in vivo. An anti-inflammatory vitamin, vitamin B6, suppressed macrophage infiltration into white adipose tissue and altered mRNA expression. We identified >3500 genes whose expression is significantly altered during the development of obesity in db/db mice, and compared them to the adipose tissue mRNA expression profile of mice supplemented with vitamin B6. We identified PTX3 and MMP3 as candidate genes regulated by macrophage infiltration. PTX3 and MMP3 mRNA expression in 3T3-L1 adipocytes was up-regulated by activated RAW264.7 cells and these mRNA levels were positively correlated with macrophage number in adipose tissue in vivo. Next, we screened adipose genes down-regulated by the interaction with macrophages, and isolated RASSF6 (Ras association domain family 6). RASSF6 mRNA in adipocytes was decreased by culture medium conditioned by activated RAW264.7 cells, and RASSF6 mRNA level was negatively correlated with macrophage number in adipose tissue, suggesting that adipocyte RASSF6 mRNA expression is down-regulated by infiltrated macrophages in vivo. Finally, this study also showed that decreased RASSF6 expression up-regulates mRNA expression of several genes, such as CD44 and high mobility group protein HMGA2. These data provide novel insights into the biological significance of interactions between adipocytes and macrophages in adipose tissue during the development of obesity.
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炎症会导致维生素B6的组织特异性耗竭。
影响因子：
4.9
作者：
Chiang EP;Smith DE;Selhub J;Dallal G;Wang YC;Roubenoff R
通讯作者：
Roubenoff R
影响因子：
16.8
作者：
Kaminski DA;Randall TD
通讯作者：
Randall TD
影响因子：
5.3
作者：
Jones, G. T.;Tarr, G. P.;Williams, M. J. A.
通讯作者：
Williams, M. J. A.
影响因子：
8
作者：
Allen, N. P. C.;Donninger, H.;Clark, G. J.
通讯作者：
Clark, G. J.
影响因子：
5.3
作者：
Alberti, L.;Gilardini, L.;Invitti, C.
通讯作者：
Invitti, C.