Astrocyte growth is regulated by neuropeptides through Tis 8 and basic fibroblast growth factor

J Clin Invest. 1994 Apr;93(4):1820-7. doi: 10.1172/JCI117167.


The important intracellular mechanisms of astrocyte growth are not well defined. Using an inhibitor of astrocyte proliferation, atrial natriuretic peptide (ANP), and the glial mitogen endothelin (ET-3), we sought a common pathway for growth regulation in these neural cells. In cultured fetal rat diencephalic astrocytes, ANP selectively and rapidly inhibited the Tis 8 immediate early gene and protein. After 4 h, ANP selectively inhibited the basic fibroblast growth factor (bFGF) gene and protein. ET-3 significantly stimulated both Tis 8 and bFGF mRNAs and protein, but also stimulated several other immediate early and growth factor/receptor genes. An antisense oligonucleotide to Tis 8 strongly prevented ET-stimulated thymidine incorporation, while the inhibitory action of ANP was enhanced. The Tis 8 antisense oligonucleotide also significantly reversed ET-stimulated bFGF transcription and enhanced the bFGF inhibition caused by ANP. In addition, an antisense oligonucleotide to bFGF significantly reversed the ET-stimulated thymidine incorporation and enhanced the ANP inhibition of DNA synthesis. The sequential modulation of Tis 8, followed by bFGF, provides a novel mechanism for both positive and negative regulation of astrocyte growth by endogenous neuropeptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astrocytes / drug effects*
  • Astrocytes / physiology
  • Atrial Natriuretic Factor / pharmacology*
  • Base Sequence
  • Cell Division / drug effects
  • DNA / biosynthesis
  • DNA-Binding Proteins / physiology*
  • Early Growth Response Protein 1
  • Endothelins / pharmacology*
  • Fibroblast Growth Factor 2 / physiology*
  • Humans
  • Immediate-Early Proteins*
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Endothelins
  • Immediate-Early Proteins
  • Oligonucleotides, Antisense
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Atrial Natriuretic Factor
  • DNA