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Journal of Neuroscience, Vol 12, 583-594, Copyright © 1992 by Society for Neuroscience
Transforming growth factor alpha, but not epidermal growth factor, promotes the survival of sensory neurons in vitro
A Chalazonitis, JA Kessler, DR Twardzik and RS Morrison
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York.
Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide
that is structurally homologous to epidermal growth factor (EGF) and
appears to bind to the same receptor in all systems tested previously. In
the present study, TGF alpha was found to enhance survival and neurite
outgrowth of cultured neonatal rat dorsal root ganglion (DRG) neurons in a
dose-dependent manner. This effect was observed with TGF alpha
concentrations as low as 17.8 pM. By contrast, EGF at concentrations up to
83 nM was ineffective. Moreover, EGF did not antagonize the TGF alpha
survival-promoting effect unless present in large excess (500-fold the
concentration for which TGF alpha is effective); even in this case, only
partial antagonism was achieved. Survival of neurons from nodose,
trigeminal, and sympathetic ganglia was not increased by TGF alpha. Both a
subpopulation of DRG neurons and of macrophages in the cultures bound
iodinated TGF alpha. This binding was inhibited by excess unlabeled TGF
alpha but not EGF. Our data are consistent with the possibilities that the
actions of TGF alpha on DRG neurons occur indirectly via unidentified
neurotrophic molecules other than NGF as well as directly on the neurons
themselves. Thus, TGF alpha, in contrast to EGF, may act as a survival or
maintenance factor for a subset of rat sensory neurons. Mediation of this
neurotrophic effect appears to occur via a new form of TGF alpha receptor.
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