首页> 美国卫生研究院文献>The Journal of Neuroscience >The Urokinase Plasminogen Activator Receptor (UPAR) Is Preferentially Induced by Nerve Growth Factor in PC12 Pheochromocytoma Cells and Is Required for NGF-Driven Differentiation
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The Urokinase Plasminogen Activator Receptor (UPAR) Is Preferentially Induced by Nerve Growth Factor in PC12 Pheochromocytoma Cells and Is Required for NGF-Driven Differentiation

机译:尿激酶纤溶酶原激活物受体(UPAR)是神经生长因子在PC12嗜铬细胞瘤细胞中优先诱导的并且是NGF驱动的分化所必需的

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摘要

Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A “second generation” representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.
机译:由神经生长因子(NGF)驱动的PC12嗜铬细胞瘤细胞分化是一个经过充分研究的模型,用于识别神经营养蛋白驱动的神经元分化的分子,生化和生理相关性,并确定此分化过程中特定事件的因果关系。尽管表皮生长因子(EGF)引起了PC12细胞响应NGF的许多相同的早期生化和分子变化,但EGF不会诱导PC12细胞的分子或形态分化。因此,鉴定其表达受PC12细胞中NGF与EGF差异调节的基因已被认为是对神经营养蛋白驱动的神经元分化的分子特异性的潜在见解的来源。现在,“第二代”代表性差异分析程序将尿激酶纤溶酶原激活物受体(UPAR)鉴定为PC12细胞中NGF比EGF广泛诱导的基因。 UPAR mRNA的反义寡核苷酸和针对UPAR蛋白的抗体均可阻断NGF诱导的PC12细胞的形态和生化分化。 NGF诱导的UPAR表达是后续NGF驱动的分化所必需的。

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