Nerve growth factor regulates transforming growth factor-beta 1 gene expression by both transcriptional and posttranscriptional mechanisms in PC12 cells.

PC12 cells express two transforming growth factor (TGF)-beta 1 transcripts, 1.7 and 2.5 kb in size. Other TGF-beta s are expressed at much lower levels. Incubation with nerve growth factor (NGF) produced a time- and dose-dependent increase in content of TGF-beta 1 transcripts. The level of the smaller mRNA increased little, whereas that of the 2.5-kb transcript increased more, with the latter becoming the predominant TGF-beta 1 message. NGF differentially regulated the stability of both mRNAs. The half-life of the 2.5-kb transcript was not altered by NGF; however, the half-life of the 1.7-kb mRNA was approximately 6 h and increased to > 30 h on incubation with NGF. In addition, induction of the 2.5-kb TGF-beta 1 mRNA by NGF required de novo protein synthesis, whereas induction of the 1.7-kb TGF-beta 1 mRNA was independent of protein synthesis. The NGF effect was independent of protein kinase C activation, which also preferentially induced the larger transcript. PC12 cells release a significant amount of TGF-beta 1, and incubation with NGF further increases TGF-beta 1 production. This factor is released in a latent form. These results indicate that an increase in expression and secretion of TGF-beta 1 accompanies neuronal differentiation in PC12 cells. Regulation of TGF-beta 1 gene expression by NGF is complex, involving both increased transcription of the TGF-beta 1 gene and stabilization of the smaller TGF-beta 1 transcript.