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.
Cosgaya
J M
JM
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Aranda
A
A
D000818:Animals; D001681:Biological Assay; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D006207:Half-Life; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D016716:PC12 Cells; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D009414:Nerve Growth Factors; D010703:Phorbol Esters; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta