Rm. Hu et Er. Levin, ASTROCYTE GROWTH IS REGULATED BY NEUROPEPTIDES THROUGH TIS-8 AND BASIC FIBROBLAST GROWTH-FACTOR, The Journal of clinical investigation, 93(4), 1994, pp. 1820-1827
The important intracellular mechanisms of astrocyte growth are not wel
l defined. Using an inhibitor of astrocyte proliferation, atrial natri
uretic peptide (ANP), and the glial mitogen endothelin (ET-3), we soug
ht a common pathway for growth regulation in these neural cells. In cu
ltured fetal rat diencephalic astrocytes, ANP selectively and rapidly
inhibited the Tis 8 immediate early gene and protein. After 4 h, ANP s
electively inhibited the basic fibroblast growth factor (bFGF) gene an
d 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 t
he bFGF inhibition caused hy ANP. In addition, an antisense oligonucle
otide to bFGF significantly reversed the ET-stimulated thymidine incor
poration and enhanced the ANP inhibition of DNA synthesis. The sequent
ial modulation of Tis 8, followed by bFGF, provides a novel mechanism
for both positive and negative regulation of astrocyte growth by endog
enous neuropeptides.