title: Transforming growth factor beta as a neuronoglial signal during peripheral nervous system response to injury.
abstract: 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 (TGF beta), a pleiotropic growth factor implicated in wound healing processes and in carcinogenesis. This TGF beta is tentatively identified as the beta-1 isoform. Adult rat DRG neurons release a biologically active form of TGF beta which is able to elicit multiple Schwann cell responses including a stimulation to proliferate. Moreover, purified TGF beta-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 TGF beta-1 stimulates type IV collagen mRNA expression in Schwann cells. This subtype of collagen is associated with the process of myelinization. Finally, TGF beta-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 TGF beta 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.
authors.affiliation: Department of Human Physiology, University of Liège, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Rogister
authors.forename: P
authors.initials: P
authors.lastname: Delrée
authors.forename: P
authors.initials: P
authors.lastname: Leprince
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Sadzot
authors.forename: B
authors.initials: B
authors.lastname: Malgrange
authors.forename: C
authors.initials: C
authors.lastname: Munaut
authors.forename: J M
authors.initials: JM
authors.lastname: Rigo
authors.forename: P P
authors.initials: PP
authors.lastname: Lefebvre
authors.forename: J N
authors.initials: JN
authors.lastname: Octave
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D010960:Plasminogen Activators / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
chemical_list: D003470:Culture Media; D016326:Extracellular Matrix Proteins; D009414:Nerve Growth Factors; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D010960:Plasminogen Activators