Wnt5b partially inhibits canonical Wnt/β-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes
Wnt5b partially inhibits canonical Wnt/β-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes
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DOI：
10.1016/j.bbrc.2005.03.007
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发表时间：
2005-05-06
影响因子：
3.1
通讯作者：
Maeda, S
中科院分区：
文献类型：
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作者：
Kanazawa, A;Tsukada, S;Maeda, S
为了阐明Wnt5b在脂肪形成中的功能作用，我们使用微阵列分析表征了过表达Wnt5b的3T3-L1细胞的基因表达谱。在筛选的2万个基因中，我们发现在过表达Wnt5b的3T3-L1细胞中，85个基因上调，211个基因下调。在Wnt5b调控的基因中，已知被WNT1 / β -catenin信号上调的胰岛素样生长因子-1 （IGF-1）、血管内皮生长因子-c （VEGF-C）和WNT1诱导信号通路蛋白1 （WISP-1）在过表达Wnt5b的细胞中表达降低。该结果随后被实时定量RT-PCR证实（IGF-1; 0.74 +/- 0.08和0.56 +/- 0.08,WISP-1; 0.71 +/- 0.03和0.56 +/- 0.08,VEGF-C; 0.67 +/- 0.01和0.80 +/- 0.07，平均SEM，分别与诱导分化后0天和2天的对照相比）。我们还发现Wnt5b在3T3-L1前脂肪细胞中的过表达能够部分阻止Wnt3a对脂肪形成的抑制作用。此外，Wnt5b的过表达能够抑制wnt3a诱导的典型Wnt/ β -catenin通路的激活，这可以通过减少β -catenin在细胞核中的易位来证明。这些发现表明，Wnt5b可能通过拮抗典型的Wnt/ β -连环蛋白途径，至少在一定程度上促进3T3-L1细胞的脂肪形成。(c) 2005爱思唯尔公司版权所有。
To elucidate the functional roles of Wnt5b in adipogenesis, we characterized gene expression profiles in Wnt5b overexpressing 3T3-L1 cells using microarray analysis. Of the similar to 20,000 genes screened, we found that 85 genes were up-regulated and 211 genes were clown-regulated in 3T3-L1 cells overexpressing Wnt5b. Among the genes regulated by Wnt5b, the expressions of insulin like growth factor-1 (IGF-1), vascular endothelial growth factor-C (VEGF-C), and WNT1 inducible signaling pathway protein 1 (WISP-1), which were known to be up-regulated by Wnt1/beta-catenin signaling, were decreased in the Wnt5b overexpressing cells. This result was subsequently confirmed by real-time quantitative RT-PCR (IGF-1; 0.74 +/- 0.08 and 0.56 +/- 0.08, WISP-1; 0.71 +/- 0.03 and 0.56 +/- 0.08, and VEGF-C; 0.67 +/- 0.01 and 0.80 +/- 0.07, mean SEM, compared with the control at zero and two days after induction of differentiation, respectively). We also found that Wnt5b overexpression in 3T3-L1 preadipocytes was able to partially prevent the inhibitory effect of Wnt3a on adipogenesis. Furthermore, the overexpression of Wnt5b was able to inhibit Wnt3a-induced activation of the canonical Wnt/beta-catenin pathway as evidenced by the reduced translocation of beta-catenin into the nucleus. These findings indicate that Wnt5b may promote adipogenesis in 3T3-L1 cells, at least in part, by antagonizing the canonical Wnt/beta-catenin pathway. (c) 2005 Elsevier Inc. All rights reserved.