The effects of transforming growth factor (TGF)-beta1 on expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, TrkB, in neurons cultured from the cerebral cortex of 18-day-old embryonic rats were examined. BDNF mRNA was significantly increased from 24-48 hr after the TGF-beta1 treatment over 20 ng/ml. Accumulation of BDNF protein in the culture medium was also potentiated by TGF-beta1, although the intracellular content of BDNF was nearly unchanged. The enhancement of BDNF mRNA expression was suppressed by the co-presence of decorin, a small TGF-beta-binding proteoglycan that inhibits the biological activities of TGF-betas. mRNA expression of full-length TrkB, the bioactive high-affinity receptor for BDNF, was also upregulated after treatment with TGF-beta1. These observations suggest that: 1) TGF-beta1 potentiates BDNF/TrkB autocrine or local paracrine system; and 2) the neurotrophic activity of TGF-beta1 is partly responsible for the BDNF induced by TGF-beta1 itself. To test this latter possibility, we examined the neuronal survival activity of TGF-beta1 with or without K252a, a selective inhibitor of Trk family tyrosine kinases. TGF-beta1 significantly enhanced neuronal survival, but the co-presence of K252a completely suppressed the activity, demonstrating the involvement of Trk receptor signaling in TGF-beta1-mediated neuronal survival in cultured rat cortical neurons. These results seem to be in line with recent findings by other investigators that some neurotrophic factors including BDNF require TGF-betas as a cofactor to exert their neurotrophic activities.
Copyright 2001 Wiley-Liss, Inc.