Modulation of Schwann cell phenotype by TGF-beta1

The phenotype of a fully differentiated, mature Schwann cell is
appar-ently largely determined by Schwann cell-axon interactions.
In vitro, elevation of intra-cellular cAMP levels in Schwann cells
induces a phenotype which resembles that of a mature, i.e.,
axon-related, Schwann cell. Therefore, an important role for cAMP
as a second messenger of axon-Schwann cell interactions in vivo is
assumed. However, the effects of cAMP on Schwann cells are not
restricted to induction of features of a mature phenotype. For
example, elevation of intracellular cAMP levels results of also in
a markedly increased synthesis of nerve growth factor (NGF) mRNA,
which is barely detectable in intact sciatic nerves of adult
animals. Furthermore, since cAMP induces myelin gene expression in
cultured Schwann cells, additional regulatory mechanisms have to be
postulated for the induction and maintenance of a mature
non-myelinating Schwann cell phenotype. Here we show that a soluble
protein growth factor can partially induce a non-myelinating mature
Schwann cell phenotype in vitro. Treatment with transforming growth
factor 1 (TGF-1) results in a marked and rapid downregulation of
the low affinty NGF receptor (NGFR) on cultured Schwann cells
without induction of PO gene expression. In contrast, in agreement
with previous studies, an increase in PO mRNA levels and a
reduction in NGFR mRNA after cAMP elevation is much slower when
compared with the effect of TGF-1, suggesting the involvement of
different intracellular mechanisms. Consistent with this
hypothesis, we did not observe an induction of mRNA coding for TGR-
isoforms after cAMP elevation in cultured Schwann cells which
constitutively synthesize TGF-1 mRNA