Identification of a new secretory factor, CCDC3/Favine, in adipocytes and endothelial cells
Identification of a new secretory factor, CCDC3/Favine, in adipocytes and endothelial cells
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DOI：
10.1016/j.bbrc.2009.12.142
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发表时间：
2010-01-29
影响因子：
3.1
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Kobayashi, Sachiko;Fukuhara, Atsunori;Shimomura, Iichiro
血管系统分泌许多生物活性因子。在基因芯片数据库中，我们搜索了在小鼠主动脉中特异性表达的具有信号序列的新基因，并集中于先前命名为CCDC 3（NCBI核苷酸条目NM_028804）的一个基因，我们将其命名为Favine（far/vessel-derived secretory protein）。北方印迹分析显示，CCDC 3在主动脉和脂肪组织中表达丰富。肥胖db/db小鼠脂肪组织中CCDC 3的mRNA水平高于对照小鼠，并且在大鼠原代脂肪细胞分化过程中被诱导。在分化的脂肪细胞中，胰岛素和吡格列酮（一种PPARgamma激动剂）可增强CCDC 3 mRNA的表达，而TNF-α、异丙肾上腺素和去甲肾上腺素可抑制CCDC 3 mRNA的表达。瞬时表达实验，随后的N-末端氨基酸序列分析显示，CCDC 3蛋白分泌到培养基中，这是剂量依赖性地减少布雷菲德菌素A，高尔基体介导的分泌途径的抑制剂。在COS-7细胞中表达时，CCDC 3蛋白被转录后修饰为N-糖基化，并形成二聚体复合物。这些结果表明，CCDC 3是由脂肪细胞和内皮细胞分泌的蛋白质，并且其水平受到饮食和营养的调节。(C)2009 Elsevier Inc. All rights reserved.
The vascular system secretes many bioactive factors. In a gene chip database, we searched for novel genes with signal sequences that are specifically expressed in murine aorta, and focused on one gene previously named CCDC3 (NCBI nucleotide entry NM_028804), and we designated as Favine (far/vessel-derived secretory protein). Northern blot analysis revealed that CCDC3 was expressed abundantly in the aorta and adipose tissues. The mRNA levels of CCDC3 were higher in adipose tissues of obese db/db mice than control mice, and induced during differentiation of rat primary adipocytes. In differentiated adipocytes, CCDC3 mRNA expression was enhanced by insulin and pioglitazone, a PPARgamma agonist, and suppressed by TNF-alpha, isoproterenol and norepinephrine. Transient expression experiments followed by N-terminal amino acid sequence analysis revealed secretion of CCDC3 protein into the Culture medium, which was dose-dependently reduced by brefeldin A, an inhibitor of Golgi-mediated secretory pathway. When expressed in COS-7 cells, CCDC3 protein was post-transcriptionally modified with N-glycosylation, and formed a dimer complex. These results indicate that CCDC3 is a protein secreted by adipocytes and endothelial cells, and that its level is regulated both hormonally and nutritionally. (C) 2009 Elsevier Inc. All rights reserved.