TRANSFORMING GROWTH-FACTOR-BETA HAS NEUROTROPHIC ACTIONS ON SENSORY NEURONS INVITRO AND IS SYNERGISTIC WITH NERVE GROWTH-FACTOR

Transforming growth factor β (TGFβ) influences the growth and differentiation of a wide variety of nonneuronal cells (nnc) during embryogenesis and in response to wounding. In the present study TGFβ1 and TGFβ2 were examined for their neurotrophic actions on neonatal rat dorsal root ganglion (DRG) neurons with ganglionic nnc in dissociated cultures. TGFβ1 and TGFβ2 each increased both neuronal survival and levels of the peptide neurotransmitter substance P (SP) expressed per neuron as well as per culture. TGFβ1 was maximally effective at a concentration of 40 pM, whereas TGFβ2 was about 10-fold less potent. Survival effects promoted by simultaneous treatment with both factors were not additive. TGFβ1 also changed the morphology and distribution of DRG nnc which resulted in clustering of DRG neurons on top of the nnc. Cotreatment of the cultures with two different anti-nerve growth factor (NGF) antibodies eliminated the neurotrophic effects of TGFβ1. However, treatment with TGFβ1 did not alter NGF mRNA expression in the cultures nor did it change the amount of NGF in the medium. Further, TGFβ1 greatly enhanced survival effects and SP stimulation promoted by exogenous NGF at concentrations up to 100 ng/ml. The neurotrophic effects of TGFβ1 were significantly attenuated by decreasing the proportion of the ganglionic nnc, suggesting a role for these cells in mediating TGFβ1 action on the neurons. It is hypothesized that the neurotrophic activity of TGFβ depended upon the presence of molecules immunologically related to NGF and that the effects of TGFβ were synergistic with NGF. These observations suggest that TGFβ may play a role in the differentiation and regeneration of DRG neurons in vivo. © 1992.