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Nerve Growth Factor Regulates Transforming Growth Factor‐β1 Gene Expression by Both Transcriptional and Posttranscriptional Mechanisms in PC12 Cells
Author(s) -
Cosgaya Jose Miguel,
Aranda Ana
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65062484.x
Subject(s) - nerve growth factor , transforming growth factor , messenger rna , biology , gene expression , growth factor , microbiology and biotechnology , gene , protein biosynthesis , medicine , endocrinology , receptor , biochemistry
PC12 cells express two transforming growth factor (TGF)‐β1 transcripts, 1.7 and 2.5 kb in size. Other TGF‐βs are expressed at much lower levels. Incubation with nerve growth factor (NGF) produced a time‐ and dose‐dependent increase in content of TGF‐β1 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‐β1 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 ∼6 h and increased to >30 h on incubation with NGF. In addition, induction of the 2.5‐kb TGF‐β1 mRNA by NGF required de novo protein synthesis, whereas induction of the 1.7‐kb TGF‐β1 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‐β1, and incubation with NGF further increases TGF‐β1 production. This factor is released in a latent form. These results indicate that an increase in expression and secretion of TGF‐β1 accompanies neuronal differentiation in PC12 cells. Regulation of TGF‐β1 gene expression by NGF is complex, involving both increased transcription of the TGF‐β1 gene and stabilization of the smaller TGF‐β1 transcript.