NGF and proNGF activate functionally distinct mRNAs in PC12 cells: an early gene expression profiling

The biological activities of NGF and of its precursor proNGF are quite distinct, due to different receptor binding profiles, but nothing is known about how proNGF regulates gene expression. We performed experiments to address this question, by verifying whether a proNGF specific transcriptional signature, distinct from that of NGF, could be identified. To this aim, we studied gene expression regulation by proNGF and NGF in PC12 cells incubated for 1 and 4 hours with recombinant NGF and proNGF, in its wild-type or in a furin-cleavage resistant form. mRNA expression profiles were analyzed by whole genome microarrays at these early time points, in order to identify specific profiles of NGF and proNGF.神经生长因子（Nerve Growth Factor，NGF）及其前体proNGF（前体神经生长因子）的生物学活性因受体结合谱的差异而截然不同，但目前尚无关于proNGF如何调控基因表达的相关研究。本研究旨在解答该科学问题，通过验证是否可鉴定出与NGF截然不同的proNGF特异性转录特征，开展了相关实验。为此，我们以PC12细胞为研究模型，分别使用重组NGF以及野生型或弗林蛋白酶（furin）切割抗性型的重组proNGF对细胞进行孵育，孵育时长分别为1小时与4小时，以此探究proNGF与NGF对基因表达的调控作用。随后，在这两个早期时间点通过全基因组微阵列（whole genome microarrays）分析信使RNA（messenger RNA，mRNA）表达谱，以鉴定NGF与proNGF各自的特异性表达特征。