D'Mello S R, Heinrich G
Evans Department of Clinical Research, University Hospital, Boston, MA 02118.
J Neurochem. 1990 Aug;55(2):718-21. doi: 10.1111/j.1471-4159.1990.tb04192.x.
Nerve injury leads to activation of fibroblasts, including stimulation of nerve growth factor (NGF) gene expression. Although interleukin-1 has been implicated as a mediator of NGF gene induction, the underlying mechanisms are not known. We investigated whether 12-O-tetradecanoyl phorbol 13-acetate (TPA), also a known stimulator of protein kinase C, regulates NGF gene expression. We show here that TPA stimulates NGF mRNA in mouse kidney and L929 fibroblasts but not in dispersed salivary cells. NGF mRNA stimulation in L929 cells is delayed by 2 h, is transient, and is followed by a parallel increase in NGF secretion. The induction of NGF mRNA is inhibited by cycloheximide, NGF mRNA levels decrease to similar values after 4 h of incubation with actinomycin D alone or in combination with TPA. These results indicate that the TPA response is cell specific and suggest that it is mediated at the transcriptional level via newly synthesized protein.
神经损伤会导致成纤维细胞活化，包括刺激神经生长因子（NGF）基因表达。尽管白细胞介素-1被认为是NGF基因诱导的介质，但其潜在机制尚不清楚。我们研究了同样是蛋白激酶C已知刺激剂的12-O-十四酰佛波醇-13-乙酸酯（TPA）是否调节NGF基因表达。我们在此表明，TPA刺激小鼠肾脏和L929成纤维细胞中的NGF mRNA，但不刺激分散的唾液细胞中的NGF mRNA。L929细胞中NGF mRNA的刺激延迟2小时，是短暂的，随后NGF分泌平行增加。环己酰亚胺抑制NGF mRNA的诱导，单独或与TPA联合用放线菌素D孵育4小时后，NGF mRNA水平降至相似值。这些结果表明TPA反应具有细胞特异性，并表明它是通过新合成的蛋白质在转录水平介导的。
