TRANSFORMING GROWTH-FACTOR-BETA AS A NEURONOGLIAL SIGNAL DURING PERIPHERAL NERVOUS-SYSTEM RESPONSE TO INJURY

In contrast to the central nervous system (CNS), the peripheral nervous system (PNS) displays an important regenerative ability which is dependent, at least in part, on Schwann cell properties. The mechanisms which stimulate Schwann cells to adapt their behavior after a lesion to generate adequate conditions for PNS regeneration remain unknown. In this work, we report that adult rat dorsal root ganglion (DRG) neurons are able, after a lesion performed in vivo or when they are dissociated and cultured in vitro, to synthesize transforming growth factor beta (TGFbeta), a pleiotropic growth factor implicated in wound healing processes and in carcinogenesis. This TGFbeta is tentatively identified as the beta-1 isoform. Adult rat DRG neurons release a biologically active form of TGFbeta which is able to elicit multiple Schwann cell responses including a stimulation to proliferate. Moreover, purified TGFbeta-1 produces a Schwann cell morphology alteration and decreases the secretion of tissue-type plasminogen activator (tPA) and enhances the secretion of plasminogen activator inhibitor (PAI) by Schwann cells. This generates conditions which are thought to favor a successful neuritic regrowth. Furthermore, purified TGFbeta-1 stimulates type IV collagen mRNA expression in Schwann cells. This subtype of collagen is associated with the process of myelinization. Finally, TGFbeta-1 decreases nerve growth factor (NGF) mRNA expression by Schwann cells, an effect which could participate in the maintenance of a distoproximal NGF gradient during nerve regeneration. We propose that neuronal TGFbeta plays an essential role as a neuronoglial signal that modulates the response of Schwann cells to injury and participates in the successful regeneration processes observed in the PNS.