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首页> 外文期刊>Cell biology international. >Altered signal transduction in Folr1-/- mouse embryo fibroblasts.
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Altered signal transduction in Folr1-/- mouse embryo fibroblasts.

机译:Folr1-/-小鼠胚胎成纤维细胞信号转导改变。

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摘要

Mice lacking the gene for Folr1 (folic acid receptor 1) have an NTD (neural tube defect) that is rescued by maternal folate supplementation. Primary cultures of MEFs (mouse embryonic fibroblasts) were established from these embryos and the effect on various signalling pathways examined. TGFbeta1 (transforming growth factor beta1) inhibited the proliferation of wild-type and Folr1-/- MEFs, and folate restriction, either in growth medium or through folate uptake, led to further inhibition of growth. This effect may be Smad-independent because reporter assays using the Smad-dependent reporter, p3TP-lux, revealed attenuation of TGFbeta1/Smad signalling in Folr1-/- MEFs. Signalling through the canonical Wnt pathway, measured by Wnt-3a stimulated expression of the target gene, Axin2, demonstrated increased activity in Folr1-/- MEFs. Only minor changes in the expression of a panel of TGFbeta (transforming growth factor beta) and Wnt pathway-associated genes were revealed when Folr1-/- MEFs were compared with wild-type cells. These results demonstrate that under conditions of reduced folate (Folr-/-) signalling, pathways crucial for proper development of the neural tube are significantly altered.
机译:缺少Folr1(叶酸受体1)基因的小鼠患有NTD(神经管缺陷),可通过补充母体叶酸来挽救它。从这些胚胎建立了MEF(小鼠胚胎成纤维细胞)的原代培养,并考察了其对各种信号通路的影响。 TGFbeta1(转化生长因子beta1)抑制野生型和Folr1-/-MEF的增殖,叶酸限制,无论是在生长培养基中还是通过叶酸摄取,都导致进一步的生长抑制。此效果可能与Smad无关,因为使用Smad依赖性报道基因p3TP-lux进行的报道基因分析显示Folr1-/-MEF中TGFbeta1 / Smad信号的减弱。通过Wnt-3a刺激的靶基因Axin2表达测量的经典Wnt途径信号表明,Folr1-/-MEFs的活性增强。当将Folr1-/-MEF与野生型细胞进行比较时,仅揭示了一组TGFbeta(转化生长因子β)和Wnt途径相关基因的表达的微小变化。这些结果表明,在减少叶酸(Folr-/-)信号的条件下,对神经管的正常发育至关重要的途径被显着改变。

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