ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.
ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.
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DOI：
10.1016/j.neuroscience.2010.12.039
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发表时间：
2011-03-17
期刊：
影响因子：
3.3
通讯作者：
Hegg CC
中科院分区：
文献类型：
--
作者：
Jia C;Cussen AR;Hegg CC
多种神经营养因子在嗅上皮的增殖、分化和存活中发挥作用，然而，信号级联反应尚未完全阐明。我们检验了ATP诱导两种神经营养因子成纤维细胞生长因子2（FGF 2）和转化生长因子α（TGFα）的合成和分泌，以及这些神经营养因子在诱导增殖中的作用的假设。与溶剂对照组相比，鼻内滴注ATP后20 h，成年Swiss韦伯斯特小鼠的FGF 2和TGFα蛋白水平升高。用嘌呤能受体拮抗剂磷酸吡哆醛-6-偶氮苯基-20，40-二磺酸（PPADS）鼻内给药可显著阻断ATP诱导的这种增加，表明FGF 2和TGFα表达的上调是由嘌呤能受体激活介导的。但在新生小鼠中，鼻内滴注ATP显著增加了FGF 2的蛋白水平，而不是TGFα。同样，ATP诱发新生小鼠嗅上皮切片分泌FGF 2，而不是TGFα，PPADS显著阻断ATP诱发的FGF 2释放。为了确定FGF 2和TGFα在诱导增殖中的作用，在成人嗅上皮中检测5-溴-2-脱氧尿苷（BrdU）掺入。鼻内给药FGF受体抑制剂PD 173074或表皮生长因子受体抑制剂AG 1478后，ATP滴注显着阻断ATP诱导的BrdU掺入。总的来说，这些数据表明，ATP通过促进FGF 2和TGFα的合成及其受体的活化来诱导成年小鼠嗅上皮的增殖。这些数据表明，不同的机制调节新生儿和成人OE的神经发生，FGF 2和TGFα在整个发育过程中可能具有不同的作用。
Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium; however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development.
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影响因子：
3.3
作者：
Jia, C.;Doherty, J. P.;Crudgington, S.;Hegg, C. C.
通讯作者：
Hegg, C. C.
影响因子：
2.9
作者：
Kawauchi, S;Beites, CL;Calof, AL
通讯作者：
Calof, AL
影响因子：
6.1
作者：
Jia C;Hegg CC
通讯作者：
Hegg CC
影响因子：
5.2
作者：
Hassenkloever, Thomas;Schwartz, Peter;Manzini, Ivan
通讯作者：
Manzini, Ivan
细胞周期通过细胞外核苷酸和成纤维细胞生长因子2调节星形胶质细胞。
影响因子：
3.5
作者：
Neary, Joseph T;Kang, Yuan;Shi, You-Fang
通讯作者：
Shi, You-Fang